Rigmor Solberg

• Osoble, Nimo Mukhtar Mohamud; Lunde, Ngoc Nguyen; Jafari, Abbas; Thoresen, G. Hege; Solberg, Rigmor & Rustan, Arild Christian (2024). The cysteine protease legumain decreases glucose metabolism and enhances fatty acid uptake in human myotubes. Biochimie. ISSN 0300-9084. 231, s. 127–136. doi: 10.1016/j.biochi.2024.12.012. Fulltekst i vitenarkiv Vis sammendrag

  Skeletal muscle has an important role in whole body energy metabolism and various proteases are involved in skeletal muscle functions. We have previously identified the cysteine protease legumain in cultured human skeletal muscle cells. However, the potential role of legumain in regulation of energy metabolism remains unexplored. This study aimed to investigate cellular uptake, processing, and activation of prolegumain in human myotubes. Additionally, we sought to determine the effects of prolegumain on energy substrate metabolism in these cells. During differentiation of human myoblast to myotubes, legumain mRNA expression and activity were upregulated. Interestingly, legumain activity in myotubes was inversely correlated with the body mass index (BMI) of the obese cell donors. Myotubes exposed to conditioned medium enriched in prolegumain during the last two days of differentiation demonstrated the capacity to internalize and process prolegumain into its active form. Pre-treatment with prolegumain induced a metabolic shift towards increased fatty acid uptake in myotubes, as evidenced by elevated oleic acid uptake whereas glucose uptake and oxidation were reduced. The metabolic changes were not reversed by a legumain inhibitor, indicating a different mechanism for this effect. The metabolic alterations were accompanied by increased mRNA expression of the fatty acid transporter CD36, whereas the glucose transporter GLUT1 mRNA level remained unchanged. These findings suggest that legumain may play a regulatory role in skeletal muscle energy metabolism, highlighting its potential as a novel therapeutic target of metabolic disorders.

• Forbord, Karl Martin; Lunde, Ngoc Nguyen; Bosnjak-Olsen, Tatjana; Johansen, Harald Thidemann; Solberg, Rigmor & Jafari, Abbas (2024). Legumain is a paracrine regulator of osteoblast differentiation and mediates the inhibitory effect of TGF-β1 on osteoblast maturation. Frontiers in Endocrinology. 15. doi: 10.3389/fendo.2024.1445049. Fulltekst i vitenarkiv
• Forbord, Karl Martin; Okla, Meshail; Lunde, Ngoc Nguyen; Bosnjak, Tatjana; Arnekleiv, Guro Lorvik & Hesselson, Daniel [Vis alle 11 forfattere av denne artikkelen] (2023). The Cysteine Protease Legumain Is Upregulated by Vitamin D and Is a Regulator of Vitamin D Metabolism in Mice. Cells. 13(1). doi: 10.3390/cells13010036. Fulltekst i vitenarkiv Vis sammendrag

  Legumain is a lysosomal cysteine protease that has been implicated in an increasing amount of physiological and pathophysiological processes. However, the upstream mechanisms regulating the expression and function of legumain are not well understood. Here, we provide in vitro and in vivo data showing that vitamin D3 (VD3) enhances legumain expression and function. In turn, legumain alters VD3 bioavailability, possibly through proteolytic cleavage of vitamin D binding protein (VDBP). Active VD3 (1,25(OH)2D3) increased legumain expression, activity, and secretion in osteogenic cultures of human bone marrow stromal cells. Upregulation of legumain was also observed in vivo, evidenced by increased legumain mRNA in the liver and spleen, as well as increased legumain activity in kidneys from wild-type mice treated with 25(OH)D3 (50 µg/kg, subcutaneously) for 8 days compared to a control. In addition, the serum level of legumain was also increased. We further showed that active legumain cleaved purified VDBP (55 kDa) in vitro, forming a 45 kDa fragment. In vivo, no VDBP cleavage was found in kidneys or liver from legumain-deficient mice (Lgmn−/−), whereas VDBP was cleaved in wild-type control mice (Lgmn+/+). Finally, legumain deficiency resulted in increased plasma levels of 25(OH)D3 and total VD3 and altered expression of key renal enzymes involved in VD3 metabolism (CYP24A1 and CYP27B1). In conclusion, a regulatory interplay between VD3 and legumain is suggested.

• Lunde, Ngoc Nguyen; Osoble, Nimo Mukhtar Mohamud; Dalmao-Fernandez, Andrea; Lukacs, Alfreda Serwah; Jafari, Abbas & Singh, Sachin [Vis alle 10 forfattere av denne artikkelen] (2023). Interplay between Cultured Human Osteoblastic and Skeletal Muscle Cells: Effects of Conditioned Media on Glucose and Fatty Acid Metabolism. Biomedicines. 11:2908(11), s. 1–20. doi: 10.3390/biomedicines11112908. Fulltekst i vitenarkiv Vis sammendrag

  The interplay between skeletal muscle and bone is primarily mechanical; however, biochemical crosstalk by secreted mediators has recently gained increased attention. The aim of this study was to investigate metabolic effects of conditioned medium from osteoblasts (OB-CM) on myotubes and vice versa. Human skeletal muscle cells incubated with OB-CM showed increased glucose uptake and oxidation, and mRNA expression of the glucose transporter (GLUT) 1, while fatty acid uptake and oxidation, and mRNA expression of the fatty acid transporter CD36 were decreased. This was supported by proteomic analysis, where expression of proteins involved in glucose uptake, glycolytic pathways, and the TCA cycle were enhanced, and expression of several proteins involved in fatty acid metabolism were reduced. Similar effects on energy metabolism were observed in human bone marrow stromal cells differentiated to osteoblastic cells incubated with conditioned medium from myotubes (SKM-CM), with increased glucose uptake and reduced oleic acid uptake. Proteomic analyses of the two conditioned media revealed many common proteins. Thus, our data may indicate a shift in fuel preference from fatty acid to glucose metabolism in both cell types, induced by conditioned media from the opposite cell type, possibly indicating a more general pattern in communication between these tissues.

• Solberg, Rigmor; Lunde, Ngoc Nguyen; Forbord, Karl Martin Frøseth; Okla, Meshail; Kassem, Moustapha & Jafari, Abbas (2022). The Mammalian Cysteine Protease Legumain in Health and Disease. International Journal of Medical Sciences. 23(24). doi: 10.3390/ijms232415983. Fulltekst i vitenarkiv Vis sammendrag

  The cysteine protease legumain (also known as asparaginyl endopeptidase or δ-secretase) is the only known mammalian asparaginyl endopeptidase and is primarily localized to the endolysosomal system, although it is also found extracellularly as a secreted protein. Legumain is involved in the regulation of diverse biological processes and tissue homeostasis, and in the pathogenesis of various malignant and nonmalignant diseases. In addition to its proteolytic activity that leads to the degradation or activation of different substrates, legumain has also been shown to have a nonproteolytic ligase function. This review summarizes the current knowledge about legumain functions in health and disease, including kidney homeostasis, hematopoietic homeostasis, bone remodeling, cardiovascular and cerebrovascular diseases, fibrosis, aging and senescence, neurodegenerative diseases and cancer. In addition, this review addresses the effects of some marketed drugs on legumain. Expanding our knowledge on legumain will delineate the importance of this enzyme in regulating physiological processes and disease conditions.

• Nielsen, Erik Waage; Miller, Yoav; Brekke, Ole Lars; Grond, Joost; Duong, Anh Hoang & Fure, Hilde [Vis alle 12 forfattere av denne artikkelen] (2022). A Novel Porcine Model of Ischemia-Reperfusion Injury After Cross-Clamping the Thoracic Aorta Revealed Substantial Cardiopulmonary, Thromboinflammatory and Biochemical Changes Without Effect of C1-Inhibitor Treatment. Frontiers in Immunology. 13:852119, s. 1–12. doi: 10.3389/fimmu.2022.852119. Fulltekst i vitenarkiv Vis sammendrag

  Ischemic injury worsens upon return of blood and innate immunity including the complement system play a central role in ischemia-reperfusion injury (IRI) as in thoracic aortic surgery. Complement component1 inhibitor (C1-INH) has been shown to reduce IRI and is a broad-acting plasma cascade inhibitor. We established a new porcine model of IRI by cross-clamping the thoracic aorta and evaluated the global changes occurring in organ function, systemic inflammatory response and organ damage with or without treatment with C1-INH-concentrate. Twenty-four piglets (8.8-11.1 kg) underwent 45 minutes clamping of the thoracic aorta at the Th8 level. Upfront 12 piglets received human saline and 12 received C1-INH (250 IU/kg) intravenously. Three sham animals received thoracic opening without clamping. Reperfusion lasted 5 hours. We studied ten cardiorespiratory markers, three hematologic markers, eleven inflammatory markers, and twelve organ damage markers over the whole experimental period. Postmortem tissue homogenates from seven organs were examined for inflammatory markers and analysed by two-way repeated-measures ANOVA, area under the curve or unpaired t-tests. By excluding sham and combining treated and untreated animals, the markers reflected a uniform, broad and severe organ dysfunction. The mean and range fold change from before cross-clamp onset to maximum change for the different groups of markers were: cardiorespiratory 1.4 (0.2-3.7), hematologic 1.9 (1.2-2.7), plasma inflammatory 19.5 (1.4-176) and plasma organ damage 2.9 (1.1-8.6). Treatment with C1-INH had only a marginal effect on the IRI-induced changes, reaching statistical significance only for the plasma complement activation product TCC (p=0.0083) and IL-4 (p=0.022) and INF-α (p=0.016) in the colon tissue. In conclusion, the present novel model of porcine global IRI is forceful with regards to central markers and could generally be applicable for pathophysiological studies. C1-INH treatment had no significant effect, but the model allows for future testing of other drugs attenuating IRI globally.

• Gregersen, Ida; Michelsen, Annika; Lunde, Ngoc Nguyen; Åkerblom, Axel; Lakic, Tatevik G. & Skjelland, Mona [Vis alle 20 forfattere av denne artikkelen] (2020). Legumain in Acute Coronary Syndromes: A Substudy of the PLATO (Platelet Inhibition and Patient Outcomes) Trial. Journal of the American Heart Association (JAHA). e016360. doi: 10.1161/JAHA.120.016360. Fulltekst i vitenarkiv Vis sammendrag

  <i>Background</i> - The cysteine protease legumain is increased in patients with atherosclerosis, but its causal role in atherogenesis and cardiovascular disease is still unclear. The aim of the study was to investigate the association of legumain with clinical outcome in a large cohort of patients with acute coronary syndrome.<p><p> <i>Methods and Results</i> - Serum levels of legumain were analyzed in 4883 patients with acute coronary syndrome from a substudy of the PLATO (Platelet Inhibition and Patient Outcomes) trial. Levels were analyzed at admission and after 1 month follow‐up. Associations between legumain and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and its individual components were assessed by multivariable Cox regression analyses. At baseline, a 50% increase in legumain level was associated with a hazard ratio (HR) of 1.13 (95% CI, 1.04–1.21), <i>P</i>=0.0018, for the primary composite end point, adjusted for randomized treatment. The association remained significant after adjustment for important clinical and demographic variables (HR, 1.10; 95% CI, 1.02–1.19; <i>P</i>=0.013) but not in the fully adjusted model. Legumain levels at 1 month were not associated with the composite end point but were negatively associated with stroke (HR, 0.62; 95% CI, 0.44–0.88; <i>P</i>=0.0069), including in the fully adjusted model (HR, 0.57; 95% CI, 0.37–0.88; <i>P</i>=0.0114).<p><p> <i>Conclusions</i> - Baseline legumain was associated with the primary outcome in patients with acute coronary syndrome, but not in the fully adjusted model. The association between high levels of legumain at 1 month and decreased occurrence of stroke could be of interest from a mechanistic point of view, illustrating the potential dual role of legumain during atherogenesis and acute coronary syndrome.

• Lunde, Ngoc Dieu Nguyen; Gregersen, Ida; Ueland, Thor; Shetelig, Christian; Holm, Sverre & Kong, Xiang Yi [Vis alle 31 forfattere av denne artikkelen] (2019). Legumain is upregulated in acute cardiovascular events and associated with improved outcome – potentially related to anti-inflammatory effects on macrophages. Atherosclerosis. ISSN 0021-9150. s. 1–9. doi: 10.1016/j.atherosclerosis.2019.12.008. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims We have previously found increased levels of the cysteine protease legumain in plasma and plaques from patients with carotid atherosclerosis. This study further investigated legumain during acute cardiovascular events. Methods Circulating levels of legumain from patients and legumain released from platelets were assessed by enzyme-linked-immunosorbent assay. Quantitative PCR and immunoblotting were used to study expression, while localization was visualized by immunohistochemistry. Results In the SUMMIT Malmö cohort (n = 339 with or without type 2 diabetes and/or cardiovascular disease [CVD], and 64 healthy controls), the levels of circulating legumain were associated with the presence of CVD in non-diabetics, with no relation to outcome. In symptomatic carotid plaques and in samples from both coronary and intracerebral thrombi obtained during acute cardiovascular events, legumain was co-localized with macrophages in the same regions as platelets. In vitro, legumain was shown to be present in and released from platelets upon activation. In addition, THP-1 macrophages exposed to releasate from activated platelets showed increased legumain expression. Interestingly, primary peripheral blood mononuclear cells stimulated with recombinant legumain promoted anti-inflammatory responses. Finally, in a STEMI population (POSTEMI; n = 272), patients had significantly higher circulating legumain before and immediately after percutaneous coronary intervention compared with healthy controls (n = 67), and high levels were associated with improved outcome. Conclusions Our data demonstrate for the first time that legumain is upregulated during acute cardiovascular events and is associated with improved outcome.

• Bosnjak, Tatjana; Solberg, Rigmor; Hemati, Paya Diana; Jafari, Abbas; Kassem, Moustapha & Johansen, Harald Thidemann (2019). Lansoprazole inhibits the cysteine protease legumain by binding to the active site. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 125(2), s. 89–99. doi: 10.1111/bcpt.13230. Fulltekst i vitenarkiv
• Lunde, Ngoc Dieu Nguyen; Bosnjak, Tatjana; Solberg, Rigmor & Johansen, Harald Thidemann (2019). Mammalian legumain - A lysosomal cysteine protease with extracellular functions? Biochimie. ISSN 0300-9084. 166, s. 77–83. doi: 10.1016/j.biochi.2019.06.002. Fulltekst i vitenarkiv Vis sammendrag

  The cysteine protease legumain (asparaginyl endopeptidase, AEP) plays important roles in normal physiology but is also associated with several disorders, such as atherosclerosis, osteoporosis, cancer and neurodegenerative diseases. The functional roles of legumain have mainly been associated with the presence in lysosomes where legumain is active and mediates processing of multiple proteins, such as the conversion of single to double chain forms of cysteine cathepsins. However, in recent years, a number of studies point to extracellular roles of legumain in addition to the pivotal roles in the lysosomes. In this review, recent knowledge on novel extracellular functions of this protease will be addressed and new discoveries in relation to the diseases mentioned above will be presented.

• Lunde, Ngoc Nguyen Dieu; Haugen, Mads Haugland; Larsen, Kristina Broe Bodin; Damgaard, Ingrid; Pettersen, Solveig & Kasem, Roya [Vis alle 11 forfattere av denne artikkelen] (2017). Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions. Biochimie. ISSN 0300-9084. 139, s. 27–37. doi: 10.1016/j.biochi.2017.05.009. Fulltekst i vitenarkiv
• Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L.; Zhang, Yuxi; Chen, Li & Postert, Benno [Vis alle 16 forfattere av denne artikkelen] (2017). Legumain regulates differentiation fate of human bone marrow stromal cells and is altered in postmenopausal osteoporosis. Stem Cell Reports. ISSN 2213-6711. 8(2), s. 373–386. doi: 10.1016/j.stemcr.2017.01.003. Fulltekst i vitenarkiv Vis sammendrag

  Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

• Poreba, Marcin; Solberg, Rigmor; Rut, Wioletta; Lunde, Ngoc Nguyen Dieu; Kasperkiewicz, Paulina & Snipas, Scott J. [Vis alle 11 forfattere av denne artikkelen] (2016). Counter selection substrate library strategy for developing specific protease substrates and probes. Cell Chemical Biology. ISSN 2451-9456. 23(8), s. 1023–1034. doi: 10.1016/j.chembiol.2016.05.020. Fulltekst i vitenarkiv
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva Børresdatter; Inass, Elyouncha; Sporsheim, Bjørnar & Gregersen, Ida [Vis alle 12 forfattere av denne artikkelen] (2016). Increased levels of legumain in plasma and plaques from patients with carotid atherosclerosis. Atherosclerosis. ISSN 0021-9150. 257, s. 216–223. doi: 10.1016/j.atherosclerosis.2016.11.026. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims The cysteine protease legumain has been shown to be up-regulated in unstable atherosclerotic plaques. This study aims to further elucidate legumain in atherosclerosis, by examining legumain in plasma and carotid plaques from patients with carotid stenosis. Furthermore, legumain secretion from monocyte-derived macrophages treated with atherogenic lipids during macrophage polarization was studied. Methods Plasma levels of legumain from patients with carotid stenosis (n = 254), healthy controls (n = 91), and secreted from monocyte-derived macrophages were assessed by enzyme-linked-immunosorbent assay. Quantitative PCR and immunoblotting of legumain were performed on isolated plaques and legumain localization was visualized by immunohistochemistry and fluorescence microscopy. Monocyte-derived macrophages polarized to M1 or M2 macrophages were treated with VLDL, oxLDL or cholesterol crystals (CC) and the level of legumain analysed. Results Patients with carotid stenosis had significantly higher levels of plasma legumain compared with healthy controls (median 2.0 versus 1.5 ng/ml, respectively; p = 0.003), although there was no correlation between the level of legumain and the degree of stenosis, and legumain was not an independent factor to identify patients with carotid plaques. Moreover, patients with symptoms the last 2 months had higher expressions of mature legumain, cystatin C and E/M, and the macrophage markers CD80 (M1) and CD163 (M2). Legumain co-localized with both M1 and M2 macrophages within plaques, whereas legumain mRNA expression was significantly higher (p < 0.0001) in plaques compared to non-atherosclerotic arteries (controls). Furthermore, in vitro studies showed significantly increased secretion of legumain from pro-inflammatory M1 compared to pro-resolving M2 macrophages (p = 0.014), and particularly in M1 treated with CC. In plaques, legumain was localized to structures resembling foam cells. Conclusions Legumain is increased in both plasma and plaques of patients with carotid stenosis and might be a new and early biomarker of atherosclerosis.

• Solberg, Rigmor; Smith, Robert; Almlöf, Maria; Tewolde, Eyassu Araia; Nilsen, Hilde & Johansen, Harald Thidemann (2014). Legumain expression, activity and secretion are increased during monocyte-to-macrophage differentiation and inhibited by atorvastatin. Biological chemistry. ISSN 1431-6730. 396(1), s. 71–80. doi: 10.1515/hsz-2014-0172. Fulltekst i vitenarkiv
• Solberg, Rigmor; Smith, Robert; Almlöf, Maria; Tewolde, Eyassu Araia; Nilsen, Hilde & Johansen, Harald Thidemann (2014). Atorvastatin inhibits processing, activity and secretion of legumain in macrophages. Biological chemistry. ISSN 1431-6730. 396(1), s. 71–80. doi: 10.1515/hsz-2014-0172. Fulltekst i vitenarkiv
• Smith, Robert; Åstrand, Ove Alexander Høgmoen; Nguyen, Luan Minh; Elvestrand, Tina; Hagelin, Gunnar & Solberg, Rigmor [Vis alle 8 forfattere av denne artikkelen] (2014). Synthesis of a novel legumain-cleavable colchicine prodrug with cell-specific toxicity. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 22(13), s. 3309–3315. doi: 10.1016/j.bmc.2014.04.056. Fulltekst i vitenarkiv
• Smith, Robert; Solberg, Rigmor; Jacobsen, Linn Løkken; Voreland, Anette Larsen; Rustan, Arild & Thoresen, G. Hege [Vis alle 7 forfattere av denne artikkelen] (2014). Simvastatin inhibits glucose metabolism and legumain activity in human myotubes. PLOS ONE. 9(1:85721). doi: 10.1371/journal.pone.0085721. Fulltekst i vitenarkiv
• Berven, Lise; Solberg, Rigmor; Truong, Hoa Hong Thi; Arlov, Øystein; Aachmann, Finn Lillelund & Skjåk-Bræk, Gudmund [Vis alle 9 forfattere av denne artikkelen] (2013). Alginates induce legumain activity in RAW 264.7 cells and accelerate autoactivation of prolegumain. Bioactive Carbohydrates and Dietary Fibre. 2, s. 30–44. doi: 10.1016/j.bcdf.2013.08.003. Fulltekst i vitenarkiv
• Berven, Lise; Johansen, Harald Thidemann; Solberg, Rigmor; Kolset, Svein Olav & Samuelsen, Anne Berit C. (2013). Autoactivation of prolegumain is accelerated by glycosaminoglycans. Biochimie. ISSN 0300-9084. 95(4), s. 772–781. doi: 10.1016/j.biochi.2012.11.002. Fulltekst i vitenarkiv Vis sammendrag

  The cysteine protease legumain participates in several biological and pathological processes including tumour invasion and metastasis. Legumain is synthesized as a zymogen and undergoes pH-dependent autoactivation of the proform in order to reach an enzymatically active form. Here we demonstrate that the naturally occurring polyanionic glycosaminoglycans (GAGs) chondroitin 4-sulphate (C4S), chondroitin 6-sulphate (C6S), chondroitin 4,6-sulphate (C4,6S), heparin, heparan sulphate (HS) as well as chondroitin sulphate (CS)-derived decasaccharides accelerated the autocatalytic activation of prolegumain through ionic interactions in a concentration-, size- and time-dependent manner at pH 4.0. In contrast, at pH 5.0 only C4S and C4,6S were able to promote prolegumain activation, while CS-derived decasaccharides, C6S, heparin and HS lost their effect at this pH.

• Haugen, Mads Haugland; Johansen, Harald Thidemann; Pettersen, Solveig; Solberg, Rigmor; Brix, Klaudia & Flatmark, Kjersti [Vis alle 7 forfattere av denne artikkelen] (2013). Nuclear Legumain Activity in Colorectal Cancer. PLOS ONE. 8(1). doi: 10.1371/journal.pone.0052980. Fulltekst i vitenarkiv Vis sammendrag

  The cysteine protease legumain is involved in several biological and pathological processes, and the protease has been found over-expressed and associated with an invasive and metastatic phenotype in a number of solid tumors. Consequently, legumain has been proposed as a prognostic marker for certain cancers, and a potential therapeutic target. Nevertheless, details on how legumain advances malignant progression along with regulation of its proteolytic activity are unclear. In the present work, legumain expression was examined in colorectal cancer cell lines. Substantial differences in amounts of pro- and active legumain forms, along with distinct intracellular distribution patterns, were observed in HCT116 and SW620 cells and corresponding subcutaneous xenografts. Legumain is thought to be located and processed towards its active form primarily in the endo-lysosomes; however, the subcellular distribution remains largely unexplored. By analyzing subcellular fractions, a proteolytically active form of legumain was found in the nucleus of both cell lines, in addition to the canonical endo-lysosomal residency. In situ analyses of legumain expression and activity confirmed the endo-lysosomal and nuclear localizations in cultured cells and, importantly, also in sections from xenografts and biopsies from colorectal cancer patients. In the HCT116 and SW620 cell lines nuclear legumain was found to make up approximately 13% and 17% of the total legumain, respectively. In similarity with previous studies on nuclear variants of related cysteine proteases, legumain was shown to process histone H3.1. The discovery of nuclear localized legumain launches an entirely novel arena of legumain biology and functions in cancer.

• Johansen, Harald Thidemann & Solberg, Rigmor (2012). Extracellular functions of cystein proteases. I Karamanos, Nikos K (Red.), Extracellular matrix: Pathobiology and signaling. De Gruyter Brill. ISSN 9783110258769. s. 239–260. doi: 10.1515/9783110258776.239. Fulltekst i vitenarkiv
• Smith, Robert; Johansen, Harald Thidemann; Nilsen, Hilde; Haugen, Mads Haugland; Pettersen, Solveig & Mælandsmo, Gunhild [Vis alle 8 forfattere av denne artikkelen] (2012). Intra- and extracellular regulation of activity and processing of legumain by cystatin E/M. Biochimie. ISSN 0300-9084. 94(12), s. 2590–2599. doi: 10.1016/j.biochi.2012.07.026. Fulltekst i vitenarkiv
• Briggs, Jon; Haugen, Mads Haugland; Johansen, Harald Thidemann; Riker, Adam I; Abrahamson, Magnus & Fodstad, Øystein [Vis alle 8 forfattere av denne artikkelen] (2010). Cystatin E/M suppresses legumain activity and invasion of human melanoma. BMC Cancer. 10(1), s. 17–17. doi: 10.1186/1471-2407-10-17. Fulltekst i vitenarkiv Vis sammendrag

  Background High activity of cysteine proteases such as legumain and the cathepsins have been shown to facilitate growth and invasion of a variety of tumor types. In breast cancer, several recent studies have indicated that loss of the cysteine protease inhibitor cystatin E/M leads to increased growth and metastasis. Although cystatin E/M is normally expressed in the skin, its role in cysteine protease regulation and progression of malignant melanoma has not been studied. Methods A panel of various non-melanoma and melanoma cell lines was used. Cystatin E/M and C were analyzed in cell media by immunoblotting and ELISA. Legumain, cathepsin B and L were analyzed in cell lysates by immunoblotting and their enzymatic activities were analyzed by peptide substrates. Two melanoma cell lines lacking detectable secretion of cystatin E/M were transfected with a cystatin E/M expression plasmid (pCST6), and migration and invasiveness were studied by a Matrigel invasion assay. Results Cystatin E/M was undetectable in media from all established melanoma cell lines examined, whereas strong immunobands were detected in two of five primary melanoma lines and in two of six lines derived from patients with metastatic disease. Among the four melanoma lines secreting cystatin E/M, the glycosylated form (17 kD) was predominant compared to the non-glycosylated form (14 kD). Legumain, cathepsin B and L were expressed and active in most of the cell lines, although at low levels in the melanomas expressing cystatin E/M. In the melanoma lines where cystatin E/M was secreted, cystatin C was generally absent or expressed at a very low level. When melanoma cells lacking secretion of cystatin E/M were transfected with pCST6, their intracellular legumain activity was significantly inhibited. In contrast, cathepsin B activity was not affected. Furthermore, invasion was suppressed in cystatin E/M over-expressing melanoma cell lines as measured by the transwell Matrigel assay. Conclusions These results suggest that the level of cystatin E/M regulates legumain activity and hence the invasive potential of human melanoma cells.

• Solberg, Rigmor; Aas, Vigdis; Thoresen, G. Hege; Kase, Eili Tranheim; Drevon, Christian A & Rustan, Arild [Vis alle 7 forfattere av denne artikkelen] (2005). Leptin expression in human primary skeletal muscle cells is reduced during differentiation. Journal of Cellular Biochemistry. ISSN 0730-2312. 96(1), s. 89–96. Fulltekst i vitenarkiv
• Aas, Vigdis; Kase, Eili Tranheim; Solberg, Rigmor; Jensen, Jørgen & Rustan, Arild (2004). Chronic hyperglycaemia promotes lipogenesis and triacylglycerol accumulation in human skeletal muscle cells. Diabetologia. ISSN 0012-186X. 47, s. 1452–1461. Fulltekst i vitenarkiv
• Yaqub, Sheraz; Solhaug, Vigdis; Vang, Torkel; Solberg, Rigmor; Aasen, Ansgar Oddne & Tasken, Kjetil [Vis alle 7 forfattere av denne artikkelen] (2003). A human whole blood model of LPS-mediated suppression of T-cell activation. Medical Science Monitor. ISSN 1234-1010. 9(BR), s. 120–126. Fulltekst i vitenarkiv
• Yaqub, Sheraz; Solhaug, Vigdis; Vang, Torkel; Solberg, Rigmor; Aasen, Ansgar Oddne & Tasken, Kjetil [Vis alle 7 forfattere av denne artikkelen] (2003). A human whole blood model of LPS mediated suppression on T cell activation. Medical Science Monitor. ISSN 1234-1010. s. 120–126. Fulltekst i vitenarkiv
• Saugstad, Ola Didrik; Ramji, S; Irani, S. F.; El-Meneza, S; Hernandez, E. A. & Vento, M [Vis alle 10 forfattere av denne artikkelen] (2003). Resuscitation of newborn infants with 21% or 100% oxygen: follow-up at 18 to 24 months. Pediatrics. ISSN 0031-4005. 11(2), s. 296–300. Fulltekst i vitenarkiv Vis sammendrag

  esuscitation of newborn infants with 21% or 100% oxygen: follow-up at 18 to 24 months. Saugstad OD, Ramji S, Irani SF, El-Meneza S, Hernandez EA, Vento M, Talvik T, Solberg R, Rootwelt T, Aalen OO. Department of Pediatric Research, Rikshospitalet, University of Oslo, Oslo, Norway. o.d.saugstad@klinmed.uio.no OBJECTIVE: To follow-up children who had been resuscitated at birth with either 21% or 100% oxygen (O2). METHODS: A multicenter study with 10 participating centers recruited 609 infants to the Resair 2 study where resuscitation was performed with either 21% or 100% O2. A follow-up between ages 18 and 24 months was performed. However, during follow-up registration, it was found that 18 infants had been enrolled twice in the original Resair 2 study with different registration numbers, leaving 591 enrolled in the Resair 2 study and 410 enrolled in the 7 centers participating in the follow-up. Of these 410 infants, 79 died (76 in the neonatal and 3 in the postneonatal period). Furthermore, for 8 infants informed consent was not obtained, leaving 323 eligible for follow-up. Of these, 213 infants (66%) were followed-up: 91 (62%) had been resuscitated with 21% O2, and 122 (69%) with 100% O2. At a median age of 22 and 20 months (not significant) in the 21% and 100% groups, respectively, a simple questionnaire was filled out and neurologic assessment was performed in addition to measuring anthropometric data. RESULTS: There were no significant differences in weight, height, or head circumference between the 2 groups. Cerebral palsy developed in 10% and 7%, respectively, in the 2 groups (not significant). In total, 11 cases (12%) in the 21% versus 11 cases (9%) in the 100% O(2) group (odds ratio: 1.39, 95% confidence interval: 0.57-3.36) developed cerebral palsy and/or mental or other delay. Furthermore, it was concluded that 14 (15%) in the 21% group and 12 (10%) in the 100% group were not normal (odds ratio: 1.67, 95% confidence interval: 0.73-3.80). CONCLUSIONS: There were no significant differences in somatic growth or neurologic handicap at an age of 18 to 24 months in infants resuscitated with either 21% or 100% O2 at birth. Based on these data, resuscitation with ambient air seems to be safe, at least in most cases. More studies are needed to settle this issue.

• Scholz, Tim; Solberg, Rigmor; Okkenhaug, Cecilie; Videm, Vibeke; Gallimore, Michael J. & Mathisen, Øystein [Vis alle 11 forfattere av denne artikkelen] (2002). The significance of heparin-coated veno-venous bypass circuits in liver transplantation. Perfusion. ISSN 0267-6591. 17, s. 45–50. Fulltekst i vitenarkiv
• Scholz, Tim; Solberg, Rigmor; Okkenhaug, Cecilie; Videm, Vibeke; Gallimore, J Michael & Mathisen, Øystein [Vis alle 12 forfattere av denne artikkelen] (2001). Veno-venous bypass in liver transplantation: heparin coated perfusion circuits reduce the activation of humoral defence systems in an in vitro model. Perfusion. ISSN 0267-6591. s. 285–292. Fulltekst i vitenarkiv
• Wang, Jacob Edward; Jørgensen, Pål Foyn; Almlöf, Maria; Thiemmermann, Christoph; Foster, Simon J & Aasen, Ansgar Oddne [Vis alle 7 forfattere av denne artikkelen] (2001). Peptidoglycan primes for the LPS-induced release of proinflammatory cytokines in whole human blood. Shock. ISSN 1073-2322. 16(3), s. 178–182. Fulltekst i vitenarkiv
• Scholz, Tim; Solberg, Rigmor; Okkenhaug, Cecilie; Videm, Vibeke; Gallimore, Michael J. & Mathisen, Øystein [Vis alle 12 forfattere av denne artikkelen] (2001). Veno-venous bypass in liver transplantation: heparin-coated perfusion circuits reduce the activation of humoral defense systems in an in vitro model. Perfusion. ISSN 0267-6591. 16(4), s. 285–292. Fulltekst i vitenarkiv Vis sammendrag

  We studied the effects of bypass circuit surface heparinization on kallikrein-kinin, coagulation, fibrinolytic and complement activation in a closed model system for simulating veno-venous bypass (VVBP) in liver transplantation (OLT). The circuits were identical to those in routine use during clinical OLT in our institution. Fresh whole human blood diluted 1:2 with Ringer's acetate was circulated at non-pulsatile flow (2 L/min) and at a constant temperature (37.5°C) for 12 hours. In 10 experiments, the entire inner surface of the circuits was coated with end-point attached heparin (HC). In the remaining 10, non-treated PVC tubings were used (NC). Components of the plasma kallikrein-kinin, coagulation, fibrinolytic and complement systems were analyzed using functional techniques (chromogenic peptide substrate assays) and enzyme immunoassays at baseline, 3 and 12 h. Significant activation of the initial (C3bc) and terminal (TCC) components of the complement system was found in both the NC and HC groups after 3 and 12 h: C3bc: NC: baseline = 4 (3.5-7.7), 3 h = 17.3* (12.5-27), 12 h = 31* (17.7-63.6), HC: baseline = 4.9 (3.2-6.8), 3 h = 9* (6-14.4), 12 h = 13.7* (7.4-18.1). TCC: NC: baseline = 0.4 (0.2-0.6), 3 h = 5* (0.8-11.9), 12 h: 13.1* (4.2-25.7). HC: baseline = 0.5 (0.1-0.6), 3 h = 0.6* (0.1-0.8), 12 h = 1.2* (0.3-2) AU/ml; median and range, (*: p<0.05). The C3bc and TCC concentrations were significantly higher in the NC group at 3 and 12 h, compared to the HC group: C3bc (NC vs. HC group): 3 h, p<0.001; 12 h, p<0.001. TCC (NC vs. HC group): 3 h, p<0.001; 12 h, p<0.001. Significant increases in values of thrombin-antithrombin complexes (p=0.003), prothrombin fragment 1+2 (p=0.006) and plasmin-a2-antiplasmin complexes (p=0.016) were found in the non-coated group, but not in the heparin-coated group during the observation period, showing that also the coagulation and fibrinolytic systems were activated in the non-coated circuits. We conclude that heparin-coating of the internal surface of the extracorporeal perfusion circuit used for VVBP reduces activation of the plasma cascade systems in a closed venous system in vitro.

Se alle arbeider i NVA

• Thoresen, G. Hege; Simonsen, terje; Christensen, Hege; Johansen, Harald Thidemann; Kase, Eili Tranheim & Robertsen, Ida [Vis alle 9 forfattere av denne artikkelen] (2021). Basal farmakologi. Fagbokforlaget. ISBN 9788245033557. 405 s. Fulltekst i vitenarkiv
• Thoresen, G. Hege; Solberg, Rigmor; Johansen, Harald Thidemann; Kase, Eili Tranheim; Rustan, Arild Christian & Christensen, Hege [Vis alle 7 forfattere av denne artikkelen] (2020). Illustrert farmakologi. Fagbokforlaget. ISBN 9788245033564. 392 s. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Solberg, Rigmor (2023). Drugs and new pharmacological targets in the treatment of osteoporosis. Fulltekst i vitenarkiv
• Alrawaf, Firas; Nilsen, Hilde; Lunde, Ngoc Nguyen; Morland, Cecilie & Solberg, Rigmor (2022). The cysteine protease legumain in Parkinson’s disease. Fulltekst i vitenarkiv
• Antobreh, Alfreda Serwah; Lunde, Ngoc Nguyen; Nilsen, Hilde & Solberg, Rigmor (2022). Effects of conditioned media from skeletal muscle cells on metabolism and regulation of the cysteine protease legumain in differentiating osteoblasts. Fulltekst i vitenarkiv
• Ciyow, Nasra; Bosnjak, Tatjana; Nilsen, Hilde; Lunde, Ngoc Nguyen; Johansen, Harald Thidemann & Solberg, Rigmor (2020). Effekt av teriparatid på differensiering og regulering av cysteinproteaser i osteoblaster. Fulltekst i vitenarkiv
• Olsen, Kristine Løkke; Johansen, Harald Thidemann; Nilsen, Hilde; Solberg, Rigmor & Berg, Kristian (2020). Effekt av cysteinproteasen legumain på celleviabilitet etter fotodynamisk terapi. Fulltekst i vitenarkiv
• Mohanachandran, Arthii; Bosnjak, Tatjana; Nilsen, Hilde; Lunde, Ngoc Nguyen; Solberg, Rigmor & Johansen, Harald Thidemann (2020). Differensiering av RAW264.7 til osteoklaster og karakterisering av cysteinproteaser i osteoklaster. Fulltekst i vitenarkiv
• Awale, Mustafa; Bosnjak, Tatjana; Nilsen, Hilde; Solberg, Rigmor & Johansen, Harald Thidemann (2019). Effekten av kjønnshormoner på differensiering av stamceller til osteoblaster og regulering av cysteinproteasene legumain og cathepsin B. Fulltekst i vitenarkiv
• Solberg, Rigmor (2019). The proteolytic enzyme legumain: Structure and functions. Fulltekst i vitenarkiv
• Bosnjak, Tatjana; Solberg, Rigmor; Arnekleiv, Guro L.; Nilsen, Hilde; Jafari, Abbas & Bassatne, A. [Vis alle 9 forfattere av denne artikkelen] (2019). Vitamin D3 upregulates legumain in the early phase of osteoblast differentiation. Fulltekst i vitenarkiv
• Gjonbalaj, Nora; Nilsen, Hilde; Solberg, Rigmor & Johansen, Harald Thidemann (2018). Effekt av inflammasjon på regulering av cysteinproteasene legumain og cathepsin B under differensiering av humane mesenkymale stamceller til osteoblaster. Fulltekst i vitenarkiv
• Abbas, Iram; Nilsen, Hilde; Johansen, Harald Thidemann & Solberg, Rigmor (2018). Deksametason hemmer differensiering av humane mesenkymale stamceller til osteoblaster og regulerer cysteinproteasene legumain og cathepsin B. Fulltekst i vitenarkiv
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva Børresdatter; Elyouncha, Inass; Sporsheim, Bjørnar & Gregersen, Ida [Vis alle 12 forfattere av denne artikkelen] (2018). Plasma and plaques from patients with carotid atherosclerosis have increased levels of legumain. Fulltekst i vitenarkiv
• Solberg, Rigmor (2018). Hvordan settes positive dopinganalyser i medisinsk/farmakologisk sammenheng, og hvordan omsettes dette til dom? Fulltekst i vitenarkiv
• Bosnjak, Tatjana; Hemati, Paya Diana; Solberg, Rigmor & Johansen, Harald Thidemann (2018). Cysteine proteases as Targets for Proton Pump Inhibitors (PPIs). Fulltekst i vitenarkiv
• Lunde, Ngoc Nguyen Dieu; Gregersen, Ida; Holm, Sverre; Michelsen, Annika; Sporsheim, Bjørnar & Espevik, Terje [Vis alle 9 forfattere av denne artikkelen] (2018). Platelet-derived legumain, a cysteine protease involved in atherosclerosis. Fulltekst i vitenarkiv
• Bosnjak, Tatjana; Hemati, Paya Diana; Nilsen, Hilde; Solberg, Rigmor & Johansen, Harald Thidemann (2017). Legumain as a target for proton pump inhibitors (PPIs): Importance for off-target effects of PPIs? Fulltekst i vitenarkiv
• Solberg, Rigmor; Bosnjak, Tatjana; Nilsen, Hilde; Jafari, Abbas; Kassem, Moustapha & Johansen, Harald Thidemann (2017). Regulation of legumain and cysteine cathepsins during differentiation of human bone marrow stromal cells towards osteoblasts. Fulltekst i vitenarkiv
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva B.; Elyoncha, Inass; Sporsheim, Bjørnar & Gregersen, Ida [Vis alle 12 forfattere av denne artikkelen] (2017). Plasma and plaques from patients with carotid atherosclerosis have increased levels of legumain. Fulltekst i vitenarkiv
• Arnekleiv, Guro L.; Nilsen, Hilde; Lunde, Ngoc Nguyen Dieu; Solberg, Rigmor & Johansen, Harald Thidemann (2017). Effekt av vitamin D3 på uttrykk, aktivitet og sekresjon av cysteinproteasen legumain studert i ulike cellemodeller. Fulltekst i vitenarkiv
• Hemati, Paya Diana; Bosnjak, Tatjana; Nilsen, Hilde; Lunde, Ngoc Nguyen Dieu; Johansen, Harald Thidemann & Solberg, Rigmor (2017). The Proton Pump Inhibitor Lansoprazole Inhibits Protease Activity of Legumain. Fulltekst i vitenarkiv
• Solberg, Rigmor & Johansen, Harald Thidemann (2016). Involvement of the cysteine protease legumain in human health and disease. Fulltekst i vitenarkiv
• Larsen, Kristina Broe Bodin; Johansen, Harald Thidemann; Solberg, Rigmor & Lunde, Ngoc Nguyen Dieu (2016). Betydning av glykosylering for internalisering og aktivering av prolegumain i humane tykktarmskreftceller. Fulltekst i vitenarkiv
• Solberg, Rigmor; Rut, Wioletta; Lunde, Ngoc Nguyen Dieu; Kasperkiewicz, Paulina; Snipas, Scott J. & Mihelic, Marko [Vis alle 11 forfattere av denne artikkelen] (2016). New Selective Probes to Inhibit and Image Legumain in Living Cells. Fulltekst i vitenarkiv
• Røsjø, Bjarne & Solberg, Rigmor (2016). Desillusjonert over dopingbruken i idretten. [Internet]. titan.uio.no. Fulltekst i vitenarkiv
• Abdukadir, Nuriddin; Lunde, Ngoc Nguyen Dieu; Nilsen, Hilde; Solberg, Rigmor & Johansen, Harald Thidemann (2016). Regulering av cysteinproteaser ved differensiering av monocytter til makrofager. Fulltekst i vitenarkiv
• Lunde, Ngoc Nguyen Dieu; Dahl, Tuva Børresdatter; Abdukadir, Nuriddin; Halvorsen, Bente; Solberg, Rigmor & Johansen, Harald Thidemann (2016). Increased secretion of legumain from pro-inflammatory M1 compared to M2 macrophages. Fulltekst i vitenarkiv
• Lunde, Ngoc Nguyen Dieu; Nilsen, Hilde; Damgaard, Ingrid; Kasem, Roya; Solberg, Rigmor & Haugen, Mads Haugland [Vis alle 7 forfattere av denne artikkelen] (2015). Importance of glycosylation for legumain and cystatin E/M functions. Fulltekst i vitenarkiv
• Johansen, Harald Thidemann; Elyouncha, Inass; Lunde, Ngoc Nguyen Dieu; Williams, Rich; Solberg, Rigmor & Nilsen, Hilde [Vis alle 7 forfattere av denne artikkelen] (2015). Opposing effects of glucose on legumain and cysteine cathepsins. Fulltekst i vitenarkiv
• Solberg, Rigmor; Poreba, Marcin; Rut, Wioletta; Kasperkiewicz, Paulina; Snipas, Scott & Turk, Boris [Vis alle 8 forfattere av denne artikkelen] (2015). Novel legumain-specific activity based probes binds and inhibits legumain in living cells. Fulltekst i vitenarkiv
• Solberg, Rigmor (2015). Novel legumain specific cell-permeable activity based probes. Fulltekst i vitenarkiv
• Berven, Lise; Solberg, Rigmor & Samuelsen, Anne Berit C. (2014). Effects of alginates on legumain Activity in RAW 264.7 cells and on prolegumain autoactivation. Planta Medica. ISSN 0032-0943. 80(16), s. 1358–1358. doi: 10.1055/s-0034-1394502. Fulltekst i vitenarkiv
• Smith, Robert; Johansen, Harald Thidemann; Jacobsen, Linn Løkken; Voreland, Anette Larsen; Rustan, Arild & Thoresen, G. Hege [Vis alle 7 forfattere av denne artikkelen] (2013). Simvastatin inhibits legumain activity and processing in human myotubes. Fulltekst i vitenarkiv
• Johansen, Harald Thidemann; Solberg, Rigmor; Nilsen, Hilde & Smith, Robert (2013). Effects and interplay of legumain and cystatin E/M om migration and invasion of macrophages. Fulltekst i vitenarkiv
• Smith, Robert; Johansen, Harald Thidemann; Nilsen, Hilde & Solberg, Rigmor (2013). Effects and interplay of legumain and cystatin E/M on migration and invasion of macrophages. Fulltekst i vitenarkiv
• Haugen, Mads Haugland; Flatmark, Kjersti; Tamhane, Tripti; Boye, Kjetil; Pettersen, Solveig & Solberg, Rigmor [Vis alle 9 forfattere av denne artikkelen] (2013). Nuclear localized legumain in colorectal cancer. Fulltekst i vitenarkiv
• Ånonsen, Kjersti Bergh; Nilsen, Hilde; Smith, Robert; Johansen, Harald Thidemann & Solberg, Rigmor (2013). Regulering av legumain i samspillet mellom makrofager og kreftceller. Fulltekst i vitenarkiv
• Voreland, Anette; Smith, Robert; Thoresen, G. Hege; Johansen, Harald Thidemann & Solberg, Rigmor (2013). The cysteine protease legumain is downregulated by simvastatin in primary human skeletal muscle cells. Fulltekst i vitenarkiv
• Tina, Elvestrand; Åstrand, Ove Alexander; Smith, Robert; Rongved, Pål; Nilsen, Hilde & Solberg, Rigmor [Vis alle 7 forfattere av denne artikkelen] (2013). Cellular effects of a colchicine-prodrug cleaved by legumain. Fulltekst i vitenarkiv
• Smith, Robert; Johansen, Harald Thidemann; Nilsen, Hilde; Yassen, Islam M.; Haugen, Mads Haugland & Pettersen, Solveig [Vis alle 9 forfattere av denne artikkelen] (2012). SECRETION, INTERNALIZATION AND INTERPLAY OF LEGUMAIN AND CYSTATIN E/M. Fulltekst i vitenarkiv
• Berven, Lise; Johansen, Harald Thidemann; Solberg, Rigmor; Kolset, Svein Olav & Samuelsen, Anne Berit C. (2012). INTERACTIONS BETWEEN PROLEGUMAIN AND GLYCOSAMINOGLYCANS. Fulltekst i vitenarkiv
• Jacobsen, Linn Løkken; Smith, Robert; Thoresen, G. Hege; Solberg, Rigmor & Johansen, Harald Thidemann (2012). Are the cysteine proteases legumain and cathepsins involved in statin-induced myotoxicity? Fulltekst i vitenarkiv
• Tran, Anny T.; Smith, Robert; Solberg, Rigmor & Johansen, Harald Thidemann (2012). Effects of atorvastatin on regulation of protease activities in macrophages. Fulltekst i vitenarkiv
• Haugen, Mads Haugland; Mælandsmo, Gunhild; Johansen, Harald Thidemann; Solberg, Rigmor; Pettersen, Solveig & Boye, Kjetil [Vis alle 7 forfattere av denne artikkelen] (2011). Nuclear activity of the cysteine protease legumain in colorectal carcinoma. Fulltekst i vitenarkiv
• Johansen, Harald Thidemann; Smith, Robert; Tewolde, Eyassu; Nilsen, Hilde & Solberg, Rigmor (2011). ATORVASTATIN INHIBITS LEGUMAIN ACTIVITY IN AND PROLEGUMAIN SECRETION FROM HUMAN ACTIVATED MACROPHAGES. Fulltekst i vitenarkiv
• Smith, Robert; Johansen, Harald Thidemann & Solberg, Rigmor (2011). Cellular localization and interplay between legumain and its endogenous inhibitor cystatin E/M. Fulltekst i vitenarkiv
• Smith, Robert; Johansen, Harald Thidemann; Nilsen, Hilde; Yassen, Islam M.; Haugen, Mads Haugland & Pettersen, Solveig J. [Vis alle 7 forfattere av denne artikkelen] (2011). SUBCELLULAR LOCALIZATION, INTERPLAY AND SECRETION OF LEGUMAIN AND CYSTATIN E/M IN HEK 293 CELLS. Fulltekst i vitenarkiv
• Haugen, Mads Haugland; Johansen, Harald Thidemann; Solberg, Rigmor; Flatmark, Kjersti & Mælandsmo, Gunhild M (2009). Expression and activity of the cysteine protease legumain in colorectal carcinoma cell lines. Fulltekst i vitenarkiv
• Briggs, Jon; Haugen, Mads Haugland; Johansen, Harald Thidemann; Riker, Adam I; Abrahamson, Magnus & Fodstad, Øystein [Vis alle 8 forfattere av denne artikkelen] (2009). Cystatin E/M suppresses legumain activity and invasion of human melanoma. Fulltekst i vitenarkiv
• Solberg, Rigmor; Almlöf, Maria; Nilsen, Hilde; Ali, Zana Abdullrahman; Abrahamson, Magnus & Johansen, Harald Thidemann (2009). Asparaginyl endopeptidase activity is upregulated during differentiation of monocytes to macrophages but only partly mediated by legumain. Fulltekst i vitenarkiv
• Omar, Sakina Ben; Johansen, Harald Thidemann; Aukrust, Pål; Halvorsen, Bente & Solberg, Rigmor (2008). Lysosomal cysteine proteases in atherosclerosis: Do inflammatory modulators regulate expression and activity? Fulltekst i vitenarkiv
• Solberg, Rigmor; Nilsen, Hilde; Johansen, Harald Thidemann; Mælandsmo, Gunhild M. & Briggs, Jon (2007). SCREENING OF THE EXPRESSIONS OF LEGUMAIN AND ITS SPECIFIC INHIBITOR CYSTATIN M IN VARIOUS MELANOMA CELLS. Fulltekst i vitenarkiv
• Almlöf, Maria; Solberg, Rigmor & Johansen, Harald Thidemann (2007). Regulation of cystein proteases in monocytes/macrophages and in tumorigenesis. Fulltekst i vitenarkiv
• Almlöf, Maria; Solberg, Rigmor; Nilsen, Hilde & Johansen, Harald Thidemann (2006). Legumain expression and activity is highly increased as monocytes differentiate toward macrophages. Fulltekst i vitenarkiv
• Almlöf, Maria; Elenjord, Renate; Solberg, Rigmor; Winberg, Jan-Olof; Loennechen, Thrina & Johansen, Harald Thidemann (2006). Malignant osteosarcoma cells express higher levels of legumain compared to non-malignant cells. Fulltekst i vitenarkiv
• Almlöf, Maria; Elenjord, Renate; Solberg, Rigmor; Winberg, Jan Olof; Loennechen, Thrina & Johansen, Harald Thidemann (2006). The expression and activity of legumain is highly increased in malignant osteosarcoma cells compared to non-malignant cells. Fulltekst i vitenarkiv
• Solberg, Rigmor (2005). FRM 2410 - Formulering og bruk av legemidler. Norges apotekerforenings tidsskrift. ISSN 0802-8400. 113(2), s. 104–105. Fulltekst i vitenarkiv
• Brekke, Stian; Rønning, Camilla; Värn, Christine; Aas, Vigdis; Thoresen, G. Hege & Solberg, Rigmor (2005). Moxonidine exhibits direct effects on human skeletal muscle cells. Fulltekst i vitenarkiv
• Barsett, Hilde & Solberg, Rigmor (2004). New curriculum for master of pharmacy, School of Pharmacy, University of Oslo, Norway. Fulltekst i vitenarkiv
• Värn, Christine; Aas, Vigdis; Endresen, Marit JR & Solberg, Rigmor (2004). Moxonidine enhances glucose uptake in human skeletal muscle cells. Fulltekst i vitenarkiv
• Yaqub, Sheraz; Solhaug, Vigdis; Vang, Torkel; Solberg, Rigmor; Aasen, Ansgar Oddne & Tasken, Kjetil [Vis alle 7 forfattere av denne artikkelen] (2002). A Human Whole Blood Model Of LPS-Mediated Suppresion Of T-Cell Activation. Fulltekst i vitenarkiv
• Rustan, Arild; Solberg, Rigmor; Reseland, Janne Elin; Andersen, Merethe H; Drevon, Christian A & Aas, Vigdis (2002). FATTY ACIDS MODULATE LEPTIN AND LEPTIN RECEPTOR (OB-RB) GENE EXPRESSION AND LEPTIN SECRETION IN CULTURED HUMAN SKELETAL MUSCLE CELLS. Fulltekst i vitenarkiv Vis sammendrag

  Leptin is a hormone primarily secreted by adipocytes that plays a pivotal role in regulating food intake, energy expenditure and neuroendocrine function. Leptin stimulates oxidation of fatty acids and uptake of glucose, and prevents accumulation of lipids in nonadipose tissues. Inducible leptin expression in skeletal muscle cells (L6 rat cells) in response to insulin and glucosamine has been reported (Wang et al., Nature 1998, 393: 684-8). Based on this observation, we examined if leptin is present in skeletal muscle cells from human biopsies, and also if leptin and its receptor (OB-RB) could be modulated by hormones, fatty acids and other energy substrates. Leptin was expressed in differentiated myotubes, and both expression (mRNA) and secretion were changed after incubation with 0.1-0.6 mM of fatty acids for 24 and 48 h. Oleate (OA) and eicosapentaenoic acid (EPA 20:5 n-3) increased leptin secretion to the culture medium, with the strongest effect of OA after 48 h incubation. We also observed that incubation with palmitate (PA), OA and EPA for 24 and 48 h increased leptin mRNA expression, whereas the leptin receptor (OB-RB) mRNA expression was reduced 40-50 % by EPA. Moreover, the effect of these fatty acids on basal and insulin-stimulated glucose metabolism was also examined. Preincubation with PA and OA (0.6 mM for 24 h) induced insulin resistance assessed by decreased insulin-stimulated 2-deoxy-glucose transport, when compared to fatty acid-free controls. EPA on the other hand, did not reduce insulin-stimulated glucose transport, and caused a 2-fold increase in basal as well as insulin-stimulated glucose transport. We have for the first time demonstrated leptin expression in human skeletal muscle cells. Furthermore, this is the first documentation of regulation of OB-RB in any tissue examined. The physiological effect of fatty acids on the leptin axis in muscle cells needs further studies. We focus on how fatty acids affect leptin, OB-RB and their signalling pathways in glucose and lipid metabolism.

• Wang, Jacob Edward; Warris, A.; Ellingsen, Espen Alme; Jørgensen, Pål Foyn; Flo, T. H. & Espevik, T [Vis alle 9 forfattere av denne artikkelen] (2001). Involvement of CD 14 and toll-like receptors in signaling by Aspergillus hypae. Fulltekst i vitenarkiv
• Wang, Jacob Edward; Warris, A.; Ellingsen, Espen Alme; Jørgensen, Pål Foyn; Flo, T. H. & Espvik, T. [Vis alle 9 forfattere av denne artikkelen] (2001). Activation of Leykocytes By Hyphal Fragments: Invvolvment of CD14 And Toll-Like Receptors. Fulltekst i vitenarkiv
• Samuelsen, Anne Berit C.; Berven, Lise; Solberg, Rigmor; Johansen, Harald Thidemann & Truong, Hong Hoa Thi (2012). Effekt av alginat på legumain, en protease involvert i kreftutvikling. Universitetet i Oslo. Fulltekst i vitenarkiv Vis sammendrag

  Bakgrunn: Alginat er en kjent polymer som har vært mye utnyttet kommersielt, men også i legemiddelbransjen de siste årene. Alginat er et løselig kostfiber som gir immunrespons ved cellestimulering. Mange studier har vist en tendens til at kosthold med mye kostfiber gir lavere insidens tykktarms-endetarmskreft. En tidligere masteroppgave ved forskningsgruppen har vist at legumainaktivitet ble påvirket av alginat ved in vitro eksperimenter, både ved direkte autoaktivering prolegumain og ved stimulering av makrofagceller. Denne oppgaven bygget videre på dette og effekten av alginat på legumain ble nærmere studert, der legumain er en cysteinprotease som har vist relasjon til kreftutvikling. Metoder: Det ble brukt forskjellige metoder for å karakterisere alginat M-60 med innhold av 60 % mannuronsyre og M-100 med 100 % mannuronsyre. Monosakkaridsammensetningen til disse alginatene ble bestemt ved metanolyse, GC, og NMR og de ble også redusert for å bestemme ladningenes betydning. Det ble utviklet en metode for å fremstille så ren alginatoligomere som mulig, ved anvendelse av alginatlyase for å degradere alginatet og deretter fraksjonering av prøvene på ionebytterkolonnen. Fraksjonene ble videre analysert på HPLC, HPAEC-PAD og MS for å bestemme størrelsen til oligomerene. Ikke redusert- og redusert M-60 og M-100, alginatlyasebehandlet M-60, og i tillegg M-75 og M-94 ble videre testet for evne til å påvirke legumainaktivitet. To ulike forhold ble studert; Stimulering av makrofager (RAW 246.7-celler) i kultur eller direkte inkubering av prolegumain sammen med de ulike alginatprøvene for å undersøke deres evne til å stimulere autoaktivering av prolegumain. Resultat: NMR-metode gav en mer nøyaktig bestemmelse av monosakkaridsammensetning til alginat i forhold til GC-metoden. Alginatdegraderingsprosessen ved behandling med alginatlyasen ble vellykket med i både buffer og vann, og vann ble derfor benyttet for å slippe å gjøre desalting. Ved direkte autoaktivering prolegumain gav de ubehandlede alginatene M-60, M-75, M-94 og M-100 øking i legumainaktiviteten. Alginat M-100 og M-94 gav mest stimulering av prolegumain autoaktivering med 7 ganger høyere legumainaktiviteten enn kontroll, mens M-60 gav 6 ganger høyere og M-75 gav 5 ganger høyere legumainaktivitet. Reduserte M-100 ga ingen stimulering av legumain autoaktivering, mens redusert M-60 og M-60 ikke fjernet borat gav 5 ganger høyere legumainaktivitet. Sammenlignet med kontrollen gav lyasebehandlet M-60-fraksjoner B2 og C4 ingen effekt, mens fraksjon B3 gav 20 % høyere og fraksjon C5 gav 40 % høyere legumainaktivitet ved autoaktiveringsforsøk. I celleforsøk gav ubehandlet alginat M-60 veldig varierende resultater. I to forsøk stimulerte den økning legumainaktivitet, men i et forsøk gjorde den ikke. M-75 og M-94 gav en hemmende effekt, der M-75 gav 50 % og M-94 gav 90 % lavere legumainaktivitet enn kontroll. M-100 gav ingen effekt. Reduserte M-60 og M-100 og de lyasebehandlede-M-60-fraksjonene gav en hemmende effekt av legumainaktivitet. Redusert M-100 gav 30 % mindre legumainaktivitet enn kontroll, men M-60 gav 50 % mindre aktivitet. Lyasebehandlet M-60- fraksjon gav 10-30 % lavere legumainaktivitet enn kontroll.

• Samuelsen, Anne Berit C.; Berven, Lise; Solberg, Rigmor; Johansen, Harald Thidemann & Nguyen, Nga Thi (2011). Studier av alginats effekt på prolegumain og cellesekresjon av matriksmetalloproteaser. Universitetet i Bergen. Fulltekst i vitenarkiv

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