Sensitivity of mouse lung fibroblasts heterozygous for GPx4 to oxidative stress

Free Radical Biology & Medicine
Michael R GarrySamir S Deeb

Abstract

Phospholipid hydroperoxide glutathione peroxidase (GPx4) is a member of the family of selenium-dependent enzymes that catalyze the reduction of cell membrane-bound phospholipid hydroperoxides in situ and thus protects against membrane damage. Overexpression of GPx4 protects cultured cells from phosphatidylcholine hydroperoxide (PCOOH)-induced loss of mitochondrial membrane potential and blocks cell death induced by treatment with various apoptotic agents. We have generated mice that are heterozygous for a GPx4 null allele (GPx4 +/-); the homozygous null genotype is embryonic lethal. We report that cultured lung fibroblasts (LFs) isolated from adult GPx4 +/- mice had approximately 50% of the GPx4 activity of LFs from GPx4 +/+ mice and were significantly more susceptible to H2O2, cadmium, and cumene hydroperoxide-induced cytotoxicity, as measured by neutral red assay. Both GPx4 +/+ and GPx4 +/- LFs were susceptible to PCOOH-induced cytotoxicity at a high PCOOH concentration. We also found that GPx4 +/- LFs have lower mitochondrial membrane potential, greater cardiolipin oxidation, and lower amounts of reduced thiols relative to GPx4 +/+ LFs, but are more resistant than GPx4 +/+ LFs to further decrements in these endpoints followi...Continue Reading

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Citations

Oct 7, 2009·Antioxidants & Redox Signaling·Marcus Conrad, Ulrich Schweizer
Mar 10, 2009·Free Radical Biology & Medicine·Shinji GotoTakahito Kondo
Mar 18, 2009·Biochimica Et Biophysica Acta·Pin Zhuo, Alan M Diamond
Sep 8, 2017·International Journal of Molecular Sciences·Do-Yeal RyuMyung-Geol Pang
May 4, 2017·Antioxidants & Redox Signaling·Matilde MaiorinoFulvio Ursini
Jul 1, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hagir B SulimanClaude A Piantadosi
May 20, 2021·Oxidative Medicine and Cellular Longevity·Ankita Sharma, Swaran Jeet Singh Flora
Nov 4, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jiaoyang TaoWeidong Fei

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