Glucose-6-phosphate dehydrogenase plays a crucial role in protection from redox-stress-induced apoptosis

A. Fico, F. Paglialunga, L. Cigliano, P. Abrescia, P. Verde, G. Martini, I. Iaccarino, S. Filosa

Research output: Contribution to journalArticlepeer-review

Abstract

Glucose-6-phosphate dehydrogenase-deleted embryonic stem (ES) cells (G6pdΔ) proliferate in vitro without special requirements, but when challenged with oxidants fail to sustain glutathione disulphide reconversion to reduced glutathione (GSH), entering a condition of oxidative stress. Here, we investigate the signalling events downstream of GSH oxidation in G6pdΔ and wild-type (wt) ES cells. We found that G6pdΔ ES cells are very sensitive to oxidants, activating an apoptotic pathway at oxidant concentrations otherwise sublethal for wt ES cells. We show that the apoptotic pathway activated by low oxidant concentrations is accompanied by mitochondria dysfunction, and it is therefore blocked by the overexpression of Bcl-XL. Bcl-XL does not inhibit the decrease in cellular GSH and reactive oxygen species formation following oxidant treatment. We also found that oxidant treatment in ES cells is followed by the activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Interestingly, ERK activation has opposite outcomes in G6pdΔ ES cells compared to wt, which has a proapoptotic function in the first and a prosurvival function in the latter. We show that this phenomenon can be regulated by the cellular GSH level.

Original languageEnglish
Pages (from-to)823-831
Number of pages9
JournalCell Death and Differentiation
Volume11
Issue number8
DOIs
Publication statusPublished - Aug 2004

Keywords

  • Apoptosis
  • G6PD deficiency
  • GSH
  • MAP kinases
  • Oxidative stress

ASJC Scopus subject areas

  • Cell Biology

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