Effects of 4-hydroxynonenal on Endoplasmic reticulum stres, apoptosis, insulin release and detoxification enzymes in pancreatic beta cells (INS-1)

4-hydroxynonenal is a products of lipid peroxidation and, at the high concentration in the cell can be form to stabil products with cellular proteins. Increased stabil products leads to unfolded protein response in endoplasmic reticulum (ER). Increased unfolded protein response or chronic ER stress can induce apoptosis and autophagy. So aim of the our study is to investigate the effects of 4-hydroxy-trans-2-nonenal in ER stress sensor proteins, detoxification enzyme profiles, apoptosis and insulin release in pancreatic beta cells (INS-1). Cell viability was decreased in time and dose dependent manner after 4-hydroxynonenal incubation in INS-1 cells. 4-hydroxynonenal alleviated basal and stimulated insulin release at high toxic dose. On the other hand 4-hydroxynonenal induced expression of detoxification enzymes such as glutathione-S-transferase (GST) and Aldose reductase (AKR1B1). 4-hydroxynonenal increased phosphorilation of PERK and levels of IRE1-a which are the markers of endoplasmic reticulum stress. At a high toxic dose, 4-hydroxynonenal leaded to CHOP and caspase 12 expression whic are effective in ER-mediated cell death. Also toxic dose 4-hydoxynonenal exposure caused to an activation on JNK, caspase 9 and caspase 3 protein expressions. As a result, 4-hydroxynonenal is effective in loss of pancreatic beta cell mass. 4-hydroxynonenal can be a factor for progression of hyperglycemia depents on insulin defficiency. Perhaps in the pre diabetic stage, antioxidant and lipid peroxide