Ngoc Nguyen Lunde

• 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 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 Dieu Nguyen; Gregersen, Ida; Ueland, Thor; Shetelig, Christian; Holm, Sverre; Kong, Xiang Yi; Michelsen, Annika; Otterdal, Kari; Yndestad, Arne; Broch, Kaspar; Gullestad, Lars; Nyman, Tuula Anneli; Bendz, Bjørn; Eritsland, Jan; Hoffmann, Pavel; Skagen, Karolina Ryeng; Gonçalves, Isabel; Nilsson, Jan; Grenegård, Magnus; Poreba, Marcin; Drag, Marcin; Seljeflot, Ingebjørg; Sporsheim, Bjørnar; Espevik, Terje; Skjelland, Mona; Johansen, Harald Thidemann; Solberg, Rigmor; Aukrust, Pål; Björbacka, Harry; Andersen, Geir Øystein & Halvorsen, Bente (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.
• Lunde, Ngoc Nguyen Dieu; Haugen, Mads Haugland; Larsen, Kristina Broe Bodin; Damgaard, Ingrid; Pettersen, Solveig; Kasem, Roya; Rut, Wioletta; Drag, Marcin; Poreba, Marcin; Johansen, Harald Thidemann & Solberg, Rigmor (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
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva Børresdatter; Inass, Elyouncha; Sporsheim, Bjørnar; Gregersen, Ida; Abbas, Azhar; Skjelland, Mona; Espevik, Terje; Solberg, Rigmor; Johansen, Harald Thidemann & Halvorsen, Bente (2017). 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.

• Poreba, Marcin; Solberg, Rigmor; Rut, Wioletta; Lunde, Ngoc Nguyen Dieu; Kasperkiewicz, Paulina; Snipas, Scott J.; Mihelic, Marko; Turk, Dusan; Turk, Boris; Salvesen, Guy S. & Drag, Marcin (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

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• 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.
• 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.
• Lunde, Ngoc Nguyen Dieu; Gregersen, Ida; Holm, Sverre; Michelsen, Annika; Sporsheim, Bjørnar; Espevik, Terje; Solberg, Rigmor; Johansen, Harald Thidemann & Halvorsen, Bente (2018). Platelet-derived legumain, a cysteine protease involved in atherosclerosis.
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva Børresdatter; Elyouncha, Inass; Sporsheim, Bjørnar; Gregersen, Ida; Abbas, Azhar; Skjelland, Mona; Espevik, Terje; Solberg, Rigmor; Johansen, Harald Thidemann & Halvorsen, Bente (2018). Plasma and plaques from patients with carotid atherosclerosis have increased levels of legumain.
• 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.
• 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.
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva B.; Elyoncha, Inass; Sporsheim, Bjørnar; Gregersen, Ida; Abbas, Azhar; Skjelland, Mona; Espevik, Terje; Solberg, Rigmor; Johansen, Harald Thidemann & Halvorsen, Bente (2017). Plasma and plaques from patients with carotid atherosclerosis have increased levels of legumain.
• Abdukadir, Nuriddin; Lunde, Ngoc Nguyen Dieu; Nilsen, Hilde; Solberg, Rigmor & Johansen, Harald Thidemann (2016). Regulering av cysteinproteaser ved differensiering av monocytter til makrofager.
• 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.
• 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.
• Solberg, Rigmor; Rut, Wioletta; Lunde, Ngoc Nguyen Dieu; Kasperkiewicz, Paulina; Snipas, Scott J.; Mihelic, Marko; Turk, Dusan; Turk, Boris; Salvesen, Guy S.; Drag, Marcin & Poreba, Marcin (2016). New Selective Probes to Inhibit and Image Legumain in Living Cells.
• Johansen, Harald Thidemann; Elyouncha, Inass; Lunde, Ngoc Nguyen Dieu; Williams, Rich; Solberg, Rigmor; Nilsen, Hilde & Halvorsen, Bente (2015). Opposing effects of glucose on legumain and cysteine cathepsins.
• Lunde, Ngoc Nguyen Dieu; Nilsen, Hilde; Damgaard, Ingrid; Kasem, Roya; Solberg, Rigmor; Haugen, Mads Haugland & Johansen, Harald Thidemann (2015). Importance of glycosylation for legumain and cystatin E/M functions.

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