Dan-Ling Chen, Jing-Nan Xiang, Li-Yong Yang
Department of Endocrinology, The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350005, China.
Biochemical and biophysical research communications 2012 Sep 28Endoplasmic reticulum (ER) stress is considered as a key factor in free fatty acid (FFA)-induced apoptosis. ERp46, a new member of the thioredoxin family, is highly expressed in pancreatic β-cells and plays an important role in glucose toxicity. In this study we examined the potential role of ERp46 in palmitic acid (PA)-induced cell apoptosis and the protective role of exendin-4, a long-acting agonist of the hormone glucagon-like peptide-1 (GLP-1) receptor. The glucose-sensitive mouse β-pancreatic cell line, βTC6, was used to investigate the mechanisms of PA-induced apoptosis. Our results showed that ERp46 expression was reduced in a dose- and time-dependent manner after PA treatment. Furthermore, inhibition of ERp46 expression by small interfering (si)RNA-mediated silencing enhanced the ER stress response via three separate pathways and increased βTC6 cell apoptosis rates. Moreover, exendin-4 reduced the ER stress response and levels of apoptosis in NC transfected cells after PA treatment, but not in cells transfected with ERp46siRNA. In conclusion, ERp46 plays a protective role in PA-induced cell apoptosis by decreasing the ER stress response and might be a novel target for anti-diabetic drugs. Exendin-4 might protect against βTC6 cell lipoapoptosis in part by activating ERp46 signaling pathway. Copyright © 2012 Elsevier Inc. All rights reserved.
Dan-Ling Chen, Jing-Nan Xiang, Li-Yong Yang. Role of ERp46 in β-cell lipoapoptosis through endoplasmic reticulum stress pathway as well as the protective effect of exendin-4. Biochemical and biophysical research communications. 2012 Sep 28;426(3):324-9
PMID: 22935416
View Full Text