15-deoxy-delta 12, 14-Prostaglandin J2 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 H2O2. We also demonstrated that the cytotoxicity caused by H2O2 could be prevented by the prostaglandin derivative, 15-deoxy-delta 12, 14-Prostaglandin J2 (15d-PGJ2).


RESULTS
Further characterization of the experimental system indicated that the half-life of H2O2 in cultures was ~1 hour. At a fixed H2O2 concentration, the cytotoxicity was dependent on the volume of H2O2 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 H2O2. The prostaglandin derivative, 15d-PGJ2, could prevent oxidative damage caused by t-butyl hydroperoxide, in addition to H2O2. Further studies indicated that both H2O2 and tBH caused an increase in reactive oxygen species and depolarization of mitochondrial membrane potential. Pretreatment of cells with 1 microM 15d-PGJ2 led to a modest decrease in reactive oxygen species generation, and a significant restoration of mitochondrial membrane potential.


CONCLUSIONS
This agent may be used in the future as a pharmacological tool for preventing cellular damage caused by oxidative stress.
Garg
Tarun K
TK
Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. gargtarunk@uams.edu
Chang
Jason Y
JY
D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000502:physiology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
C477819:15-deoxyprostaglandin J2; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D015230:Prostaglandin D2