Importance of glucose-6-phosphate dehydrogenase in the adaptive response to hydrogen peroxide in Saccharomyces cerevisiae

Abstract

Glucose-6-phosphate dehydrogenase (G6PDH)-deficient cells of Saccharomyces cerevisiae showed increased susceptibility and were unable to induce adaptation to oxidative stress. Historically, mainly in human erythrocytes, it has been suggested and accepted that decreased cellular GSH, due to loss of the NADPH-dependent activity of glutathione reductase (GR), is responsible for the increased sensitivity to oxidative stress in G6PDH-deficient cells. In the present study we investigated whether the increased susceptibility and the inability to induce adaptation to H2O2 stress of G6PDH-deficient yeast is caused by incompleteness of glutathione recycling. We constructed G6PDH- and GR-deficient mutants and analysed their adaptive response to H2O2 stress. Although G6PDH-deficient cells contained comparable amounts of GSH and GR activity to wild-type cells, GSSG was not reduced efficiently, and intracellular GSSG levels and the ratio of GSSG to total glutathione (GSSG/tGSH) were higher in G6PDH-deficient cells than in wild-type. On the other hand, GR-deficient cells showed a susceptibility identical with that of wild-type cells and induced adaptation to H2O2 stress, even though the GSSG/tGSH ratio in GR-deficient cells was higher than in G6PDH-deficient cells. These results indicate that incompleteness of glutathione recycling alone is not sufficient to account for the increased sensitivity and inability to induce adaptation to H2O2 stress of G6PDH-deficient yeast cells. In S. cerevisiae, G6PDH appears to play other important roles in the adaptive response to H2O2 stress besides supplying NADPH to the GR reaction.

Effect of Aquilegia vulgaris (L.) ethyl ether extract on liver antioxidant defense system in rats

“…G-6-P-D serves an important function in acquiring tolerance against oxidative stress since its activity is a factor limiting the rate of NADPH synthesis within the pentose phosphate pathway. NADPH is a coenzyme involved in the reduction of GSSG to GSH which is catalyzed by glutathione reductase [51]. In our experiment, the activity of G-6-P-D was decreased by APAP administration, which seems to be compatible with GSH depletion.…”

The Yeast Genes ROX1, IXR1, SKY1 and Their Effect upon Enzymatic Activities Related to Oxidative Stress

“…A previous work (Godon et al, 1998) showed that S. cerevisiae treated with H 2 O 2 is able to oxidize more glucose through the PPP than through glycolysis in order to obtain NADPH necessary in the oxidative defence reactions. In fact it has been proved that G6PDH mutants are more sensitive to oxidative stress caused by H 2 O 2 (Izawa et al, 1998;Junhke et al, 1996).…”

Posttranslational Regulation of Glucose-6-phosphate Dehydrogenase Activity in Tongue Epithelium

“…The importance of G6PD as an NADPH-supplying enzyme is increasingly acknowledged, not only for erythrocytes, which lack any other NADPH-producing route (Vulliamy et al 1993), but also for other cell types both prokaryotic (Storz and Altuvia 1994), and eukaryotic, including Saccharomyces . In the latter organism, NADPH is involved in the adaptive response to H 2 O 2 via glutathione reductase (Izawa et al 1998). Pandolfi et al (1995) have demonstrated the indispensable role of G6PD in the defense against oxidative stress in mouse embryonic stem cells, whereas supply of pentoses for nucleic acid synthesis can be entirely taken over by the transketolase-transaldolase pathway, thus bypassing G6PD.…”