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

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2010 Oct 7

PMID 20924496

Citations 7

Authors

Rui Zhang

Jin Sook Kim

Kyoung Ah Kang

Mei Jing Piao

Ki Cheon Kim

Jin Won Hyun

Affiliations

Soon will be listed here.

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.

Citing Articles

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Amelioration of streptozotocin‑induced pancreatic β cell damage by morin: Involvement of the AMPK‑FOXO3‑catalase signaling pathway.

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Discovery of a Benzamide Derivative That Protects Pancreatic β-Cells against Endoplasmic Reticulum Stress.

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CHOP Deficiency Ameliorates ERK5 Inhibition-Mediated Exacerbation of Streptozotocin-Induced Hyperglycemia and Pancreatic β-Cell Apoptosis.

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Apigenin attenuates streptozotocin-induced pancreatic β cell damage by its protective effects on cellular antioxidant defense.

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