Propofol Reduces Hydrogen Peroxide-Induced Apoptosis through Down-Regulating Bim Expression in Alveolar Epithelial Cells

Abstract

Propofol is an intravenous anesthetic agent widely used to introduce and maintain anesthesia during surgical procedures, and it has often been used in recent years as a sedative in patients with acute lung injury (ALI). A common cause of ALI is sepsis, and apoptosis in vascular endothelium and alveolar epithelial cells (AECs) during sepsis plays an important role in the pathologic formation of ALI. Propofol has drawn greater attention due to its anti-inflammatory effect and anti-apoptosis capability. It was already found that propofol inhibited MCP-1 mRNA expression and secretion, as well as the phosphorylation of p38 MAPK, SAPK/JNK, ATF-2, and c-Jun induced by lipopolysaccharide (LPS) in AECs. The present study investigated the effect and mechanism of propofol on apoptosis induced by hydrogen peroxide (H₂O₂) in AECs. AECs were treated with 0.1 or 1μMH₂O₂ for 1, 12,or 24h following pretreatment with 25μM propofol for 1h. The cell proliferation assay was performed using the TetraColor ONE. The percentage of apoptotic cells was measured by flow cytometry analysis. The phosphorylation of c-Jun and expression of Bim, Bcl-2, and Bcl-xL were measured by a Western blot analysis. Propofol down-regulated c-Jun phosphorylation and Bim (as a known c-Jun-mediated induction of pro-apoptotic and antiapoptotic target genes) expression and up-regulated the reduction of Bcl-2 and Bcl-xl expression induced by H₂O₂ in AECs. These results suggest that the application of propofol has potential to reduce apoptosis through the JNK pathway and Bim down-regulation.