New insights into redox response modulation in Fanconi's anemia cells by hydrogen peroxide and glutathione depletors.

The FEBS Journal
Paola CuccaroloPaolo Degan

Abstract

Fanconi's anemia (FA) patients face severe pathological consequences. Bone marrow failure, the major cause of death in FA, accounting for as much as 80-90% of FA mortality, appears to be significantly linked to excessive apoptosis of hematopoietic cells induced by oxidative stress. However, 20-25% of FA patients develop malignancies of myeloid origin. A survival strategy for bone marrow and hematopoietic cells under selective pressure evidently exists. This study reports that lymphoblastoid cell lines derived from two FA patients displayed significant resistance to oxidative stress induced by treatments with H(2) O(2) and various glutathione (GSH) inhibitors that induce production of reactive oxygen species, GSH depletion and mitochondrial membrane depolarization. Among the various GSH inhibitors employed, FA cells appear particularly resistant to menadione (5 μm) and ethacrynic acid (ETA, 50 μm), two drugs that specifically target mitochondria. Even after pre-treatment with buthionine sulfoximine, a GSH synthesis inhibitor that induces enhanced induction of reactive oxygen species, FA cells maintain significant resistance to these drugs. These data suggest that the resistance to oxidative stress and the altered mitochondrial a...Continue Reading

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Citations

Aug 13, 2013·Trends in Molecular Medicine·Enrico CappelliPaolo Degan
Jan 30, 2015·Scientific Reports·Cesare UsaiPaolo Degan
Jul 7, 2017·Journal of Cellular Physiology·Silvia RaveraEnrico Cappelli
Aug 28, 2014·Journal of Cellular Physiology·Silvia RaveraPaolo Degan

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