Protective Mechanism of KIOM-4 in Streptozotocin-Induced Pancreatic beta-Cells Damage Is Involved in the Inhibition of Endoplasmic Reticulum Stress

作者：Zhang Rui; Kim Jin Sook; Kang Kyoung Ah; Piao Mei Jing; Kim Ki Cheon; Hyun Jin Won^*

来源：Evidence-Based Complementary and Alternative Medicine, 2011.

DOI：10.1155/2011/231938

Endoplasmic reticulum stress-mediated apoptosis plays an important role in the destruction of pancreatic beta-cells and contributes to the development of type 1 diabetes. The present study examined the effect of KIOM-4, a mixture of four plant extracts, on streptozotocin-(STZ-) induced endoplasmic reticulum (ER) stress in rat pancreatic beta-cells (RINm5F). KIOM-4 was found to inhibit STZ-induced apoptotic cell death, confirmed by formation of apoptotic bodies and DNA fragmentation. STZ was found to induce the characteristics of ER stress; mitochondrial Ca2+ overloading, enhanced ER staining, release of glucose-regulated protein 78 (GRP78), phosphorylation of RNA-dependent protein kinase (PKR) like ER kinase (PERK) and eukaryotic initiation factor-2 alpha (eIF-2 alpha), cleavage of activating transcription factor 6 (ATF6) and caspase 12, and upregulation of CCAAT/enhancer-binding protein-homologous protein (CHOP). However, KIOM-4 attenuated these changes induced by STZ. Furthermore, KIOM4 suppressed apoptosis induced by STZ in CHOP downregulated cells using CHOP siRNA. These results suggest that KIOM-4 exhibits protective effects in STZ-induced pancreatic beta-cell damage, by interrupting the ER stress-mediated pathway.

• 出版日期2011