Abstract
BackgroundOligomannuronates (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.MethodsIn 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.ResultsOur 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.ConclusionsOM prevented mitochondrial dysfunction induced by human IAPP in RINm5F islet cells through JNK dependent signaling pathways.
Highlights
Oligomannuronates (OM) are natural products from alginate that is frequently used as food supplement
We obtained several kinds of OM with different molecular masses, and we used RINm5F cells as a model to elucidate the involvement of Jun N-terminal protein kinase (JNK) signal pathway in Human IAPP (hIAPP)-induced mitochondrial dysfunction in pancreatic beta cells, and the protective effects of OM are associated with its ability to attenuate the mitochondrial dysfunction
We found that hIAPP treatment induced intracellular Reactive Oxygen Species (ROS) generation in RINm5F cells accompanied with damages in mitochondrial function, including loss of membrane potential (MMP), depletion of ATP, release of apoptogenic factors such as cytochrome c (Cyto-c) and apoptosis inducing factor (AIF), increased expression of Bax, and decreased expression Bcl-2, which was attenuated by co-treatment with OMs
Summary
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. Islet formation is a hallmark of type 2 diabetes occurring in most patients [1, 2], which is associated with decrease beta cell function and mass. Human IAPP (hIAPP) is a peptide hormone composed of natural unstructured 37 residues that are commonly stored and secreted from the beta cell secretory granules of islets [1, 3]. Gradual loss of insulin-producing islet beta cell mass in type 2 diabetic patients leads to increased islet amyloid deposits. Synthetic hIAPP fibrils and oligomers induced apoptosis in human or rat islet beta cells. In the hIAPP transgenic mouse model, hyperglycemia causes an increase in amyloid
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