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KIOM-79 attenuated cell damage induced by endoplasmic reticulum stress by inhibiting apoptosis in RINm5F cells

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Abstract

Endoplasmic reticulum (ER) is a cellular compartment responsible for biosynthesis and folding of newly synthesized proteins destined for secretion, such as insulin. ER stress plays a role in the pathogenesis of diabetes and is associated with pancreatic β-cell damage. The aim of this study was to examine the effect of KIOM-79, a mixture of plant extracts, on streptozotocin (STZ)-induced ER stress in pancreatic RINm5F β-cells. STZ induced characteristics of ER stress; the release of Ca2+ from ER, increased ER staining, induction of glucose-regulated protein-78, phosphorylation of PKR-like ER kinase, and eukaryotic initiation factor-2α, as well as cleavage of activating transcription factor-6, whereas KIOM-79 inhibited these changes. Moreover, KIOM-79 inhibited STZ-induced apoptotic cell death. STZ induced CCAAT/enhancer-binding protein-homologous protein (CHOP) and cleavage of caspase 12, which are ER stress-induced apoptosis regulatory proteins; however, KIOM-79 suppressed these effects. KIOM-79 suppressed apoptosis induced by STZ treatment in CHOP siRNA-transfected cells. Furthermore, KIOM-79 restored cell viability decreased by STZ treatment via ER-stressed apoptosis. The pancreatic β-cells damaged by STZ had decreased levels of insulin, and KIOM-79 restored the levels. Taken together, these results suggest that KIOM-79 had cytoprotective effects against STZ-induced apoptosis by interrupting the ER stress pathway.

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Correspondence to Jin Won Hyun.

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Two authors contributed equally to this study.

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Kim, K.C., Kim, J.S. & Hyun, J.W. KIOM-79 attenuated cell damage induced by endoplasmic reticulum stress by inhibiting apoptosis in RINm5F cells. Biotechnol Bioproc E 16, 1083–1089 (2011). https://doi.org/10.1007/s12257-011-0120-9

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  • DOI: https://doi.org/10.1007/s12257-011-0120-9

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