Resveratrol Attenuates Oleic Acid-induced L02 Cell Hepatic Lipotoxicity By Modulating Bmi-1 Expression

Aims: NAFLD is caused by the definited liver other factors,apart from alcohol intake,to diffuse hepatocellular bullae fat into the main characteristics of clinical syndrome.It is one of the important reasons of chronic severe liver diseases,such as Hepatocellular Carcinoma(HCC).NAFLD is associated with the free radical generation and disruption of redox balance.Bmi1 is a component of PRC1 complex inhibiting the expression of genes,which play important roles in tissue development and cell differentiation.Bmi1 plays an important role in mediating the production of ROS,mitochondrial function and DNA damage repair(DDR).Studies demonstrated that the natural antioxidant,resveratrol,having potential of improving liver tissue and can protect from oxidative stress and hepatic mitochondria dysfunction.In this study,we take use of oleic acid-induced L02 cell hepatic lipotoxicity NAFLD model,using overexpressioned and interferred Bmi1 plasmid to transfect sub-confluent L02 cell,using western blot,qRT PCR and immunofluorescence technique,to evaluate whether resveratrol reduce the oleic acid-induced hepatic lipotoxicity by modulating Bmi-1 expression and decreasing ROS level.Methods: This study first explored if the resveratrol dose can alleviate the oleic acid-induced L02 cell hepatic lipotoxicity,metabolism of fat accumulation,toxic effects of injury and apoptosis.Furthermore,we see whether resveratrol can reduce oleic acid-induced L02 cell oxidative stress,and improve the DNA damage.Then we used western blot and qRT-PCR to demonstrate whether Bmi1 is the target of resveratrol.Finally,overexpressioned and interferred Bmi1 plasmid were transfect sub-confluent L02 cell to detect oleic acid-induced hepatic lipotoxicity,and to test the effect of resveratrol is the same of up-regulation of Bmi-1 expression.Results: Resveratrol attenuates oleic acid-induced L02 cell Hepatic Lipotoxicity and decreases ROS level.Meanwhile,resveratrol increases Bmi-1 expression while lowers the expression of its downstream pathway protein INK4A/ARF.Moreover,transfected Bmi1 siRNA to L02,cells are more likely to cause fat toxicity;But when transfected overexpressioned Bmi1 to L02,cells are more resisted to fat toxicity.Our study not only illustrates the molecular mechanism of resveratrol in relieving the occurrence and development of NAFLD as antioxidant,but also provides a theoretical support for the development of resveratrol as medicine to prevent and treat NAFLD.