15-deoxy-delta 12, 14-Prostaglandin J(2 )prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stress

BACKGROUND: With the use of cultured human retinal pigment epithelial cells, we have previously described a number of cellular responses to oxidative stress caused by H(2)O(2). We also demonstrated that the cytotoxicity caused by H(2)O(2 )could be prevented by the prostaglandin derivative, 15-deoxy-delta 12, 14-Prostaglandin J(2 )(15d-PGJ(2)). RESULTS: Further characterization of the experimental system indicated that the half-life of H(2)O(2 )in cultures was ~1 hour. At a fixed H(2)O(2 )concentration, the cytotoxicity was dependent on the volume of H(2)O(2 )solution used in the culture, such that higher volume caused more cytotoxicity. Most cells were committed to die if the culture was treated for 2 hours with a cytotoxic concentration of H(2)O(2). The prostaglandin derivative, 15d-PGJ(2), could prevent oxidative damage caused by t-butyl hydroperoxide, in addition to H(2)O(2). Further studies indicated that both H(2)O(2 )and tBH caused an increase in reactive oxygen species and depolarization of mitochondrial membrane potential. Pretreatment of cells with 1 μM 15d-PGJ(2 )led to a modest decrease in reactive oxygen species generation, and a significant restoration of mitochondrial membrane potential. CONCLUSION: This agent may be used in the future as a pharmacological tool for preventing cellular damage caused by oxidative stress.