Genipin inhibits apoptosis and endoplasmic reticulum stress induced by saturated fatty acid in HepG2 cell

Abstract

Objective To examine the protective effect of genipin from palmitate-induced cytotoxicity in HepG2 cells and investigate the underlying mechanism. Methods HepG2 cells were divided into 4groups and were treated respectively with bovine serum albumin (BSA) ,palmitate (1 mmol/L) ,genipin(20μmol/L) or palmitate for 24 h after genipin pretreatment for 30 min. Assayed the cell viability and lactate dehydrogenase enzyme (LDH) release. Flowcytometry and Hoechst staining were employed for determination of cell apoptosis after 16 h-treatment. Glucose-regulated protein( GRP)78 and CCAAT enhancer binding protein-homologous protein(CHOP) mRNA expression was quantified by real time PCR while X-box binding protein( XBP)-1 splicing was showed by PCR and electrophoresis after 6 h-treatment. Results Compared with BSA, palmitate decreased cell viability ( P ＜ 0. 05 )while increased LDH release ( P ＜ 0. 01 ). It also significantly induced apoptosis of HepG2 cell (P ＜0.05 ). Expression of GRP78 and CHOP mRNA was up-regulated by palmitate (P＜0.001), so was XBP-1 splicing. Compared with palmitate, genipin pretreatment increased cell viability (P＜0.05), reduced LDH release (P＜0.05) and inhibited apoptosis ( P ＜ 0. 01 ) of HepG2 cell. The expression of GRP78 and CHOP mRNA was decreased by genipin( P ＜ 0. 01 ). Electrophoresis of XBP-1 PCR products showed less spliced XBP-1 in genipin-palmitate treated cells than palmitate treated ones. Conclusion Genipin protects HepG2 cells from palmitate-induced cell apoptosis, which may be mediated by inhibition of endoplasmic reticulum stress. Key words: Lipotoxicity ; Genipin ; Apoptosis ; Endoplasmic reticulum stress