15–deoxy–delta 12,14–Prostaglandin J2 Prevents Oxidative Stress Induced Reactive Oxygen Species Generation and Mitochondrial Membrane Depolarizaion

Abstract

Abstract: : Purpose: With the use of cultured human RPE cells, we have previously demonstrated that the cytotoxicity caused by H2O2 could be prevented by the prostaglandin derivative, 15–deoxy–delta 12, 14–Prostaglandin J2 (15d–PGJ2). The current study was designed to study the mechanism by which this agent prevented oxidative stress induced RPE cell death. Methods: The ARPE–19 human RPE cell line was used in this study. Oxidative stress was induced by H2O2 or t–butyl hydroperoxide (tBH). Reaction oxygen species was determined by the dye, H2DCF–DA, and mitochondrial membrane potential was determined by the JC–1 dye. Cell viability was determined by the MTT assay. Results:In addition to H2O2, 15d–PGJ2 could also prevent oxidative damage caused by tBH. Both H2O2 and tBH caused an increase in reactive oxygen species and depolarization of mitochondrial membrane potential. Pretreatment of cells with 1 µM 15d–PGJ2 led to a modest decrease in reactive oxygen species generation, and a significant restoration of mitochondrial membrane potential, both of which may be partially responsible for the saving effect of 15d–PGJ2. Conclusion: This agent may be used in the future as a pharmacological tool to prevent RPE damage caused by oxidative stress.

Keywords: age–related macular degeneration • oxidation/oxidative or free radical damage • retinal pigment epithelium