Original ContributionMultiple roles of microsomal glutathione transferase 1 in cellular protection: A mechanistic study
Section snippets
Chemicals
All cell culture media and their ingredients were obtained from GIBCO BRL (Midlothian, UK). Geneticin (G418) was purchased from GE Healthcare. CuOOH was obtained from Merck. ECL kit was from Amersham Biosciences. Tert-butylhydroperoxide (BuOOH) was obtained from Riedel de Haёn (Germany). 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), dimethyl sulfoxide (DMSO), EDTA, HNE, α-tocopheryl acetate (vitamin E), and formaldehyde were all purchased from Sigma–Aldrich (St. Louis, MO,
MGST1 protects cells from lipophilic hydroperoxides
We, and others, have previously shown that MGST1 can protect cells from oxidative stress induced by hydrogen peroxide, CuOOH, or oxidized docosahexaenoic acid [22], [23]. Here we extend these findings by comparing the cellular effects of CuOOH and BuOOH, which are both substrates for MGST1. The latter, however, displays fivefold lower specific activity (data not shown). We find that MGST1 efficiently protects cells from both these organic hydroperoxides (comparing overexpressing cells to vector
Conclusion
This study shows that MGST1 is important in protecting cells and that the protection occurs by multiple mechanisms (Fig. 7). We show that MGST1-overexpressing cells are protected against substrates (CuOOH, HNE), poor substrates (BuOOH), and nonsubstrates (cisplatin). We suggest that MGST1 protects cells by direct reduction of toxicants (CuOOH/BuOOH) and downstream protection against lipid peroxidation (CuOOH/BuOOH) as well as against a toxic end-product of lipid peroxidation (HNE) by direct
Acknowledgments
This study was supported by the Swedish Research Council, AstraZeneca, and funds from the Karolinska Institutet.
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