Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

作者: Hyun-jung Yoo , Chung-Oui Hong , Sang Keun Ha , Kwang-Won Lee

DOI: 10.3390/ANTIOX9090771

关键词:

摘要: To investigate the anti-diabetic properties of chebulic acid (CA) associated with prevention methyl glyoxal (MG)-induced mitochondrial dysfunction in INS-1 pancreatic β-cells, cells were pre-treated CA (0.5, 1.0, and 2.0 μM) for 48 h then treated 2 mM MG 8 h. The effects on evaluated using following: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; glyoxalase 1 (Glo-1) expression via Western blot enzyme activity assays; Nrf-2, nuclear factor erythroid 2-related protein reactive oxygen species (ROS) production mRNA related components (UCP2, uncoupling 2; VDAC1, voltage-dependent anion-selective channel-1; cyt c, cytochrome c quantitative reverse transcriptase-PCR; membrane potential (MMP); adenosine triphosphate (ATP) synthesis; glucose-stimulated insulin secretion (GSIS) assay. viability was maintained upon pre-treating before exposure to MG. upregulated Glo-1 prevented MG-induced ROS production. Mitochondrial alleviated by pretreatment; this occurred downregulation UCP2, increase MMP ATP synthesis. Further, pre-treatment promoted recovery from decrease GSIS. These results indicated that could be employed as a therapeutic agent diabetes due its ability prevent development sensitivity oxidative stress-induced β-cells.

参考文章(42)
Shigeomi Shimizu, Masashi Narita, Yoshihide Tsujimoto, Yoshihide Tsujimoto, Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC Nature. ,vol. 399, pp. 483- 487 ,(1999) , 10.1038/20959
Jinshuang Bo, Shiya Xie, Yi Guo, Chunli Zhang, Yanming Guan, Chunmei Li, Jianxin Lu, Qing H. Meng, Methylglyoxal Impairs Insulin Secretion of Pancreatic β-Cells through Increased Production of ROS and Mitochondrial Dysfunction Mediated by Upregulation of UCP2 and MAPKs. Experimental Diabetes Research. ,vol. 2016, pp. 2029854- 2029854 ,(2016) , 10.1155/2016/2029854
Ning Li, Francesca Frigerio, Pierre Maechler, The sensitivity of pancreatic β-cells to mitochondrial injuries triggered by lipotoxicity and oxidative stress Biochemical Society Transactions. ,vol. 36, pp. 930- 934 ,(2008) , 10.1042/BST0360930
Richard Chikara Koya, Hisakazu Fujita, Shigeomi Shimizu, Makoto Ohtsu, Masato Takimoto, Yoshihide Tsujimoto, Noboru Kuzumaki, Gelsolin Inhibits Apoptosis by Blocking Mitochondrial Membrane Potential Loss and Cytochrome c Release Journal of Biological Chemistry. ,vol. 275, pp. 15343- 15349 ,(2000) , 10.1074/JBC.275.20.15343
Chen-Yu Zhang, Laura E. Parton, Chian Ping Ye, Stefan Krauss, Ruichao Shen, Cheng-Ting Lin, John A. Porco, Bradford B. Lowell, Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced β cell dysfunction in isolated pancreatic islets Cell Metabolism. ,vol. 3, pp. 417- 427 ,(2006) , 10.1016/J.CMET.2006.04.010
Annunziata Lapolla, Riccardo Flamini, Antonio Dalla Vedova, Antonella Senesi, Rachele Reitano, Domenico Fedele, Elisa Basso, Roberta Seraglia, Pietro Traldi, None, Glyoxal and Methylglyoxal Levels in Diabetic Patients: Quantitative Determination by a New GC/MS Method Clinical Chemistry and Laboratory Medicine. ,vol. 41, pp. 1166- 1173 ,(2003) , 10.1515/CCLM.2003.180
Susana Garcia de Arriba, Grant Stuchbury, Jennifer Yarin, Jim Burnell, Claudia Loske, Gerald Münch, None, Methylglyoxal impairs glucose metabolism and leads to energy depletion in neuronal cells--protection by carbonyl scavengers. Neurobiology of Aging. ,vol. 28, pp. 1044- 1050 ,(2007) , 10.1016/J.NEUROBIOLAGING.2006.05.007
F. Fiory, A. Lombardi, C. Miele, J. Giudicelli, F. Beguinot, E. Van Obberghen, Methylglyoxal impairs insulin signalling and insulin action on glucose-induced insulin secretion in the pancreatic beta cell line INS-1E Diabetologia. ,vol. 54, pp. 2941- 2952 ,(2011) , 10.1007/S00125-011-2280-8
A.M. Sadowska, B. Manuel-y-Keenoy, W.A. De Backer, Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review. Pulmonary Pharmacology & Therapeutics. ,vol. 20, pp. 9- 22 ,(2007) , 10.1016/J.PUPT.2005.12.007