Protective Mechanism of KIOM-4 in Streptozotocin-Induced Pancreatic β-Cells Damage Is Involved in the Inhibition of Endoplasmic Reticulum Stress. (16th September 2010)

• Record Type: Journal Article
• Authors: Zhang, Rui; Kim, Jin Sook; Kang, Kyoung Ah; Piao, Mei Jing; Kim, Ki Cheon; Hyun, Jin Won
• Is Part Of: Evidence-based complementary and alternative medicine. Volume 2011(2011)
• Publication Date: 2010-09-16
• Subjects: Alternative medicine -- Periodicals; 615.505
• DOI: 10.1155/2011/231938
• Languages: English
• ISSNs: 1741-427X

Abstract

Abstract : Endoplasmic reticulum stress-mediated apoptosis plays an important role in the destruction of pancreatic β -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 β -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 Ca 2+ 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-2α (eIF-2α ), 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, KIOM-4 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 β -cell damage, by interrupting the ER stress-mediated pathway.