Oligomannuronate prevents mitochondrial dysfunction induced by IAPP in RINm5F islet cells by inhibition of JNK activation and cell apoptosis

• Published in: Chinese medicine Vol. 15; no. 1; p. 27
• Main Authors: Liu, Xi, Li, Qiong, Cheng, Xiaolei, Liu, Zhichun, Zhao, Xiaoliang, Zhang, Shuai, Yu, Guangli, Zhao, Xia, Hao, Jiejie
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.03.2020; BioMed Central; BMC
• Subjects: Acids; Alginic acid; Amylin; Amyloid; Apoptosis; Apoptosis-inducing factor; Backup software; Bax protein; Bcl-2 protein; Beta cells; Cell activation; Cell growth; Cytochrome c; Cytosol; Diabetes; Dietary supplements; Islet amyloid polypeptide; Islet cells; JNK activation; Kinases; Metabolism; Mitochondria; Mitochondrial dysfunction; Molecular weight; Natural products; Oligomannuronate; Oxygen consumption; Pancreas; Pancreatic beta cells; Penicillin; Peptides; Pharmaceutical industry; RINm5F cells; Type 2 diabetes; United States > US; Japan; Type 2 diabetes; RINm5F cells; Mitochondrial dysfunction; JNK activation; Islet amyloid polypeptide; Oligomannuronate
• ISSN: 1749-8546; 1749-8546
• DOI: 10.1186/s13020-020-00310-4

Oligomannuronates (OM) are natural products from alginate that is frequently used as food supplement. The aim of this study was to investigate the in vitro protective effects of OM on RINm5F cells against human Islet amyloid polypeptide (IAPP) induced mitochondrial dysfunction, as well as the underlying mechanisms. In the present study, we obtained several kinds of OM with different molecular masses, and then we used RINm5F cells as a model to elucidate the involvement of JNK signal pathway in hIAPP-induced mitochondrial dysfunction in pancreatic beta cells, and the protective effects of OM are associated with its ability to attenuate the mitochondrial dysfunction. Our results demonstrated that human IAPP induced mitochondrial dysfunction, as evidence by loss of ΔΨm and ATP content, and decrease in oxygen consumption and complex activities, was accompanied by JNK activation, changes in the expressions of Bcl-2 and Bax proteins, release of cytochrome c (Cyto-c) and apoptosis inducing factor (AIF) from mitochondria into cytosol. Interestingly, the human IAPP induced damage in RINm5F cells were effectively restored by co-treatment of OM. Moreover, JNK activation was required for the OM mediated changes in RINm5F cells. OM prevented mitochondrial dysfunction induced by human IAPP in RINm5F islet cells through JNK dependent signaling pathways.