title: Phycocyanin prevents methylglyoxal-induced mitochondrial-dependent apoptosis in INS-1 cells by Nrf2.
abstract: Methylglyoxal (MG) is a reactive dicarbonyl compound, whose abnormal accumulation in diabetic patients exerts deleterious effects on cells and tissues. The β-cell is the main target cell of Type 2 diabetes, and its insulin secretion injury and cell apoptosis can be due to mitochondrial dysfunction. Previous studies have demonstrated MG induced β-cell apoptosis. However, little is known about the effect of MG on β-cell mitochondrial dysfunction. Phycocyanin (PC) has been demonstrated to possess various biological activities including the effects on diabetic models in vivo. The aim of this study was to determine the protective effect of PC against methylglyoxal (MG)-induced dysfunction in pancreatic β-cell INS-1 and also the mechanism. We demonstrated that MG induced mitochondrial dysfunction by the decline in ATP levels, and the increase of the level of intracellular reactive oxygen species (ROS). Furthermore, MG released cytochrome c and apoptosis-inducing factor (AIF) from the mitochondrion, induced changes in the expression of Bcl-2 family members, activated caspases and increased PARP cleavage. Interestingly, PC activated nuclear erythroid-related factor 2 (Nrf2), and Nrf2 activation as well as antioxidant enzymes HO-1 and glyoxalase 1 (Glo-1) were confirmed to be involved in the mechanisms underlying the protection of PC by RNA interference. Altogether, these results demonstrated that PC prevented mitochondrial-dependent apoptosis in MG-induced INS-1 cells and the effect was associated with Nrf2 activation.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. ouyu2008@126.com.
authors.forename: Yingnv
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. ouyu2008@126.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. ouyu2008@126.com.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wan
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. ouyu2008@126.com.
authors.forename: Xinshuo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Integrative Biology and Pharmacology, Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, USA. xiaodong.cheng@uth.tmc.edu.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. ouyu2008@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ou
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects; D007791:Lactoylglutathione Lyase / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010798:Phycocyanin / Q000494:pharmacology*; D011765:Pyruvaldehyde / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051033:Apoptosis Inducing Factor; C494826:BAX protein, human; D007328:Insulin; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D010798:Phycocyanin; D011765:Pyruvaldehyde; D045304:Cytochromes c; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C000597196:GLO1 protein, human; D007791:Lactoylglutathione Lyase