323 BVES Contributes to Colonic Wound Healing After Mechanical Injury

Abstract

G A A b st ra ct s and the affect on intracellular ROS, mitochondrial membrane potential, and cell viability were determined. The requirement of intracellular ROS in siPHB-induced autophagy was assessed using the ROS scavenger N-acetyl-L-cysteine. Results: TNFα-induced autophagy inversely correlated with PHB protein expression. Exogenous PHB expression reduced basal levels of autophagy and levels of TNFα-induced autophagy in intestinal epithelial cells. siPHB in epithelial cells induced mitochondrial autophagy via increased intracellular ROS independent of p53 signaling. Inhibition of autophagy during siPHB knockdown exacerbated mitochondrial depolarization and reduced cell viability. Conclusions: Decreased PHB levels coupled with dysfunctional autophagy renders intestinal epithelial cells susceptible to mitochondrial damage and cytotoxicity. Repletion of PHB may represent a therapeutic approach to combat oxidant and cytokine-induced mitochondrial damage in diseases such as inflammatory bowel disease.