Depending on the stage of hepatosteatosis, p53 causes apoptosis primarily through either DRAM‐induced autophagy or BAX

摘要: Background & Aims Apoptosis mediated by p53 plays a pathological role in the progression of hepatosteatosis. It is noteworthy that can promote expression damage-regulated autophagy modulator (DRAM), an inducer autophagy-mediated apoptosis. However, relationship between p53-mediated apoptosis and hepatosteatosis remains elusive. This study aimed to examine how orchestrates affect hepatosteatosis. Methods HepG2 cells were treated with oleic acid (OA) for 24 h induce Mice fed high-fat diet 20 or 40 weeks hepatosteatosis. Results OA induced dose-dependent increase steatosis severity OA also autophagy, which was critical mild 400 μM OA, but not more severe 800 1200 μM OA. inhibition siRNA mostly blocked OA-induced autophagy. Moreover, DRAM-dependent primarily occurred mitochondria (mitophagy), where DRAM localized. In mainly dependent on p53-induced BAX, localized mitochondria. Our vivo showed increased both Increased identified hepatosteatosis, whereas greater BAX observed hepatosteatosis. Conclusions p53 may via different mechanisms. DRAM-mediated mitophagy primary apoptotic induces