Acacetin antagonized lipotoxicity in pancreatic β-cells via ameliorating oxidative stress and endoplasmic reticulum stress.

Abstract

During the pathogenesis and progression of diabetes, lipotoxicity is a major threat to the function and survival of pancreatic β-cells. To battle against the lipotoxicity induced cellular damages, the present study investigated the beneficial effects of acacetin, a natural antioxidant, on free fatty acid (FFA) stressed RINm5F cells and the potential mechanism involved. RINm5F cells with or without 1h pretreatment of acacetin were treated with 0.35mM sodium palmitate for 24h. Cell viability, intracellular reactive oxygen species (ROS) level, antioxidant capacity, cellular apoptosis, and endoplasmic reticulum (ER) stress biomarker expression were investigated. Our experiments demonstrated that acacetin treatment significantly scavenged the intracellular ROS, upregulated the endogenous antioxidant enzymes, and diminished the sub-G1 DNA fraction in the cells exposed to FFA, suggesting its efficacy against oxidative stress. Meanwhile, acacetin treatment significantly mitigated the overload of intracellular Ca2+ and reduced the pro-apoptotic protein expression in the FFA stimulated cells, and thereby attenuated the ER stress-mediated cell apoptosis. Furthermore, siRNA interference results confirmed that the suppressing of C/EBP-homologous protein (CHOP) was critical to improve FFA-induced reduction in cell viability and ameliorated the ER stress caused by FFA stimulation. Acacetin may antagonize lipotoxicity in pancreatic cells by attenuating the oxidative stress and ER stress.