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

Abstract

Abstract Background 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. Methods 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. Results 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. Conclusions OM prevented mitochondrial dysfunction induced by human IAPP in RINm5F islet cells through JNK dependent signaling pathways.

Keywords

• Oligomannuronate
• Type 2 diabetes
• Islet amyloid polypeptide
• JNK activation
• Mitochondrial dysfunction
• RINm5F cells