15-deoxy-delta 12, 14-Prostaglandin J2 prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stressReportar como inadecuado




15-deoxy-delta 12, 14-Prostaglandin J2 prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stress - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Pharmacology

, 4:6

First Online: 18 May 2004Received: 26 December 2003Accepted: 18 May 2004

Abstract

BackgroundWith 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.

ResultsFurther 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 μM 15d-PGJ2 led to a modest decrease in reactive oxygen species generation, and a significant restoration of mitochondrial membrane potential.

ConclusionThis agent may be used in the future as a pharmacological tool for preventing cellular damage caused by oxidative stress.

Keywords15d-PGJ2 oxidative stress ROS reactive oxygen species MMP mitochondrial membrane potential, RPE retinal pigment epithelium. Abbreviations15d-PGJ215-deoxy-delta 12, 14-Prostaglandin J2

FCCPcarbonyl cyanide p-trifluoromethoxyphenylhydrazone

FUfluorescence units

H2DCF-DA2-, 7-dichlorodihydrofluorescein diacetate

HBSSHank-s Balanced Salt Solution

JC-15,5-, 6,6-tetrachloro-1, 1-, 3,3-tetraethylbenzimidazolocarbocyanine iodide

MMPmitochondrial membrane potential ΔΨm, MTT 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide

ODoptical density

PPARsperoxisome proliferator-activated receptors

ROSreactive oxygen species

RPEretinal pigment epithelium

tBHt-butyl hydroperoxide

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2210-4-6 contains supplementary material, which is available to authorized users.

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Autor: Tarun K Garg - Jason Y Chang

Fuente: https://link.springer.com/



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