Enhanced expression of glucose-6-phosphate dehydrogenase in human cells sustaining oxidative stress

Ursini, Matilde Valeria; Parrella, Angelina; Rosa, Graziella; Salzano, Salvatore; Martini, Giuseppe

doi:10.1042/bj3230801

Cited by 144 publications

(102 citation statements)

References 40 publications

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“…Thus, the levels of G6PD have a dramatic effect on the susceptibility to apoptotic cell death induced by both agents. DISCUSSION We have already shown that G6PD expression is up-regulated by oxidants through a mechanism acting mainly on the rate of transcription of this gene (16). Here we show that this effect is specifically counteracted by NAC, an antioxidant that replenishes the GSH pool (35).…”

Section: G6pd-mediated Rise Of Gsh Levels 2754mentioning

confidence: 59%

“…Effect Is Specifically Counteracted by NAC-We have already reported that several oxidative drugs, whose final effect is to decrease the intracellular GSH pool, enhanced the expression of G6PD and that this regulation is achieved at the levels of transcription of this gene (16). In the first experiment, human Hep3B cells were treated with diamide, a powerful sulfhydryl group-oxidizing agent that specifically causes the depletion of glutathione without any other observable effect (33).…”

Section: G6pd Expression Is Enhanced By Gsh-depleting Drugs: Thismentioning

confidence: 99%

“…or decrease the GSH pool. The mechanism regulating G6PD expression appears to affect the rate of transcription initiation (16).…”

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confidence: 99%

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Enhanced Glutathione Levels and Oxidoresistance Mediated by Increased Glucose-6-phosphate Dehydrogenase Expression

Salvemini¹,

Franzè²,

Iervolino³

et al. 1999

Journal of Biological Chemistry

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306

186

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Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose phosphate pathway that is responsible for the generation of NADPH, which is required in many detoxifying reactions. We have recently demonstrated that G6PD expression is induced by a variety of chemical agents acting at different steps in the biochemical pathway controlling the intracellular redox status. Although we obtained evidence that the oxidative stress-mediated enhancement of G6PD expression is a general phenomenon, the functional significance of such G6PD induction after oxidant insult is still poorly understood. In this report, we used a GSHdepleting drug that determines a marked decrease in the intracellular pool of reduced glutathione and a gradual but notable increase in G6PD expression. Both effects are seen soon after drug addition. Once G6PD activity has reached the maximum, the GSH pool is restored. We suggest and also provide the first direct evidence that G6PD induction serves to maintain and regenerate the intracellular GSH pool. We used HeLa cell clones stably transfected with the human G6PD gene that display higher G6PD activity than the parent HeLa cells. Although the activities of glutathione peroxidase, glutathione reductase, and catalase were comparable in all strains, the concentrations of GSH were significantly higher in G6PD-overexpressing clones. A direct consequence of GSH increase in these cells is a decreased reactive oxygen species production, which makes these cells less sensitive to the oxidative burst produced by external stimuli. Indeed, all clones that constitutively overexpress G6PD exhibited strong protection against oxidants-mediated cell killing. We also observe that NF-B activation, in response to tumor necrosis factor-␣ treatment, is strongly reduced in human HeLa cells overexpressing G6PD.

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Section: G6pd-mediated Rise Of Gsh Levels 2754mentioning

confidence: 59%

Section: G6pd Expression Is Enhanced By Gsh-depleting Drugs: Thismentioning

confidence: 99%

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Enhanced Glutathione Levels and Oxidoresistance Mediated by Increased Glucose-6-phosphate Dehydrogenase Expression

Salvemini¹,

Franzè²,

Iervolino³

et al. 1999

Journal of Biological Chemistry

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306

186

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“…Enhanced GSH levels and resistance to oxidation were demonstrated in different cells after an oxidant insult mediated by an increased G6PD expression [30,31]. An efficient level of GSH is crucial for the maintenance of an adequate metabolism, antioxidant protection of Hb, and the membrane integrity of the RBCs.…”

Section: Discussionmentioning

confidence: 99%

“…As a new result, a reduced GSH recycling capacity of the RBCs was demonstrated in the hypertensive pregnant patients, which could be a harmful factor, predisposing them to oxidative hemolysis. We suggest that a misadaptation to the normal pregnancy-induced oxidative stress in hypertensive patients may be a consequence of either a redox-sensitive inactivation of G6PD, mediated by oxidants from activated neutrophils [34], or an insufficient induction of the enzyme G6PD [31]. Fig.…”

Section: Discussionmentioning

confidence: 99%

Blood glutathione redox status in gestational hypertension

Németh

Orvos

Boda

2001

Free Radical Biology and Medicine

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Abstract-Gestational hypertension during the third trimester reflects an exaggerated maternal inflammatory response to pregnancy. We hypothesized that oxidative stress present even in normal pregnancy becomes uncompensated in hypertensive patients. A glucose-6-phosphate dehydrogenase (G6PD) activity sufficient to meet the increased reductive equivalent need of the cells is indispensable for defense against oxidative stress. The erythrocyte glutathione redox system was studied, where G6PD is the only NADPH source. The glutathione (GSH) redox status was measured both in vivo and after an in vitro oxidative challenge in pregnant women with gestational hypertension (n ϭ 19) vs. normotensive pregnant subjects (n ϭ 18) and controls (n ϭ 20). An erythrocyte GSH depletion with an increase in the oxidized form (GSSG) resulted in an elevated ratio GSSG/GSH (0.305 Ϯ 0.057; mean Ϯ SD) in hypertensive pregnant women vs. normotensive pregnant or control subjects (0.154 Ϯ 0.025; 0.168 Ϯ 0.073; p Ͻ .001). In hypertensive pregnant patients, a "GSH stability" decrease after an in vitro oxidative challenge suggested a reduced GSH recycling capacity resulting from an insufficient NADPH supply. The erythrocyte GSSG/GSH ratio may serve as an early and sensitive parameter of the oxidative imbalance and a relevant target for future clinical trials to control the effects of antioxidant treatment in women at increased risk of the pre-eclampsia syndrome.

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Cytogenetic damage and induction of pro-oxidant state in human lymphocytes exposed in vitro to gliphosate, vinclozolin, atrazine, and DPX-E9636

Lioi

Scarfì

Santoro

et al. 1998

Environ. Mol. Mutagen.

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We analyzed chromosome aberrations (CAs), sister chromatid exchanges (SCEs), mitotic index (MI), and glucose 6‐phosphate dehydrogenase (G6PD) enzyme activity in human peripheral lymphocytes from three healthy donors exposed in vitro to different concentrations of gliphosate, vinclozolin, atrazine, and DPX‐E9636. The pesticides gliphosate, vinclozolin, and atrazine have been studied in a broad range of genetic tests with predominantly conflicting or negative results, whereas little is known about the genotoxicity of DPX‐E9636. In our experimental conditions, each chemical compound tested produced a dose‐related increase in the percent of aberrant cells and an increase of SCE/cell. Furthermore, at the highest concentrations of vinclozolin, atrazine, and DPX‐E9636, we observed a significant reduction of the mitotic index. The increase of G6PD activity in exposed lymphocyte cultures strongly indicated an induction of a pro‐oxidant state of the cells as an initial response to pesticide exposure. Environ. Mol. Mutagen. 32:39–46, 1998 © 1998 Wiley‐Liss, Inc.

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Enhanced expression of glucose-6-phosphate dehydrogenase in human cells sustaining oxidative stress

Cited by 144 publications

References 40 publications

Enhanced Glutathione Levels and Oxidoresistance Mediated by Increased Glucose-6-phosphate Dehydrogenase Expression

Enhanced Glutathione Levels and Oxidoresistance Mediated by Increased Glucose-6-phosphate Dehydrogenase Expression

Blood glutathione redox status in gestational hypertension

Cytogenetic damage and induction of pro-oxidant state in human lymphocytes exposed in vitro to gliphosate, vinclozolin, atrazine, and DPX-E9636

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