Mechanism of apoptosis induced by the combined action of acrylamide and Elaidic acid through endoplasmic reticulum stress injury

Abstract

Thermal processing of food is likely to form acrylamide (AA) and elaidic acid (EA), which are both mainly metabolized by the liver. The two substances are associated with the pathogenesis of liver disease. In the current study, we investigated the toxic effects of the combined action of AA and EA on HSC-T6 cells, and the mechanism of apoptosis exacerbated by the co-exposure. The results showed a synergistic effect of AA and EA, which exacerbated the damage and oxidative stress (OS) in HSC-T6. Meanwhile, the expression of endoplasmic reticulum stress (ERS) proteins, such as GRP78 and CHOP, was increased, the ERS pathway was activated, and Ca²⁺ in cells was increased, which exacerbated mitochondrial damage, and opened IP3R-Grp75-VDAC1 channel. Both ERS and mitochondrial damage caused the process of cell apoptosis. Inhibition of ERS by 4-phenylbutyric acid (4-PBA) significantly reversed the synergistic effects on mitochondrial damage via ERS, suggesting that AA and EA exacerbated mitochondrial damage through ERS-mediated Ca²⁺ overload. AA and EA synergistically damaged the function of mitochondria through exacerbating ERS and led to cell apoptosis.

Keywords: Acrylamide (AA); Apoptosis; Elaidic acid (EA); Endoplasmic reticulum stress (ERS); HSC-T6 cells; Mitochondrial dysfunction.