Dataset Information

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

ABSTRACT:

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.

Conclusion

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

SUBMITTER: Garg TK

PROVIDER: S-EPMC446193 | biostudies-literature | 2004 May

REPOSITORIES: biostudies-literature

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Publications

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

Garg Tarun K TK Chang Jason Y JY

BMC pharmacology 20040518

<h4>Background</h4>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).<h4>Results</h4>Further characterization of the experimental system indicated that the half-life of H2O2 in cultures was ~1 hour. At a fixed H2O2 concentration, ...[more]

PMID: 15149553

Similar Datasets

Project description:15-deoxy-?(12,14)-prostaglandin J2 (15d-PGJ2) is an anti-inflammatory downstream product of the cyclooxygenase enzymes. It has been implicated to play a protective role in a variety of inflammatory mediated diseases, including rheumatoid arthritis, neural damage, and myocardial infarctions. Here we show that 15d-PGJ2 also plays a role in Salmonella infection. Salmonella enterica Typhimurium is a Gram-negative facultative intracellular pathogen that is able to survive and replicate inside phagocytic immune cells, allowing for bacterial dissemination to systemic sites. Salmonella species cause a wide range of morbidity and mortality due to gastroenteritis and typhoid fever. Previously we have shown that in mouse models of typhoid fever, Salmonella infection causes a major perturbation in the prostaglandin pathway. Specifically, we saw that 15d-PGJ2 production was significantly increased in both liver and feces. In this work we show that 15d-PGJ2 production is also significantly increased in macrophages infected with Salmonella. Furthermore, we show that the addition of 15d-PGJ2 to Salmonella infected RAW264.7, J774, and bone marrow derived macrophages is sufficient to significantly reduce bacterial colonization. We also show evidence that 15d-PGJ2 is reducing bacterial uptake by macrophages. 15d-PGJ2 reduces the inflammatory response of these infected macrophages, as evidenced by a reduction in the production of cytokines and reactive nitrogen species. The inflammatory response of the macrophage is important for full Salmonella virulence, as it can give the bacteria cues for virulence. The reduction in bacterial colonization is independent of the expression of Salmonella virulence genes SPI1 and SPI2, and is independent of the 15d-PGJ2 ligand PPAR-?. 15d-PGJ2 also causes an increase in ERK1/2 phosphorylation in infected macrophages. In conclusion, we show here that 15d-PGJ2 mediates the outcome of bacterial infection, a previously unidentified role for this prostaglandin.

Dataset Information

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

Background

Results

Conclusion

Publications

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

Similar Datasets

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