Critical role of sulfenic acid formation of thiols in the inactivation of glyceraldehyde-3-phosphate dehydrogenase by nitric oxide

Ishii, Toshiaki; Sunami, Osamu; Nakajima, Hidemitsu; Nishio, Hideaki; Takeuchi, Tadayoshi; Hata, Fumiaki

doi:10.1016/s0006-2952(99)00060-x

Cited by 82 publications

(58 citation statements)

References 42 publications

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“…25,26 These effects may be the consequence of the depletion of intracellular NAD 1 via PARP activation and/or the inactivation of GAPDH by S-nitrosylation and formation of sulfenic acid. 27 Our results show that inhibition of GAPDH is not enough to explain the dramatic drop in ATP content and the inhibition in the formation of lactate caused by ascorbate/menadione. Actually, while GAPDH activity is inhibited by about 25%, both the ATP content and the formation of lactate are inhibited by about 80%.…”

Section: Discussionmentioning

confidence: 65%

Role of glycolysis inhibition and poly(ADP‐ribose) polymerase activation in necrotic‐like cell death caused by ascorbate/menadione‐induced oxidative stress in K562 human chronic myelogenous leukemic cells

Verrax

Vanbever

Stockis

et al. 2006

Intl Journal of Cancer

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Among different features of cancer cells, two of them have retained our interest: their nearly universal glycolytic phenotype and their sensitivity towards an oxidative stress. Therefore, we took advantage of these features to develop an experimental approach by selectively exposing cancer cells to an oxidant insult induced by the combination of menadione (vitamin K 3 ) and ascorbate (vitamin C). Ascorbate enhances the menadione redox cycling, increases the formation of reactive oxygen species and kills K562 cells as shown by more than 65% of LDH leakage after 24 hr of incubation. Since both lactate formation and ATP content are depressed by about 80% following ascorbate/menadione exposure, we suggest that the major intracellular event involved in such a cytotoxicity is related to the impairment of glycolysis. Indeed, NAD 1 is rapidly and severely depleted, a fact most probably related to a strong Poly(ADP-ribose) polymerase (PARP) activation, as shown by the high amount of poly-ADP-ribosylated proteins. The addition of N-acetylcysteine (NAC) restores most of the ATP content and the production of lactate as well. The PARP inhibitor dihydroxyisoquinoline (DiQ) was able to partially restore both parameters as well as cell death induced by ascorbate/menadione. These results suggest that the PARP activation induced by the oxidative stress is a major but not the only intracellular event involved in cell death by ascorbate/menadione. Due to the high energetic dependence of cancer cells on glycolysis, the impairment of such an essential pathway may explain the effectiveness of this combination to kill cancer cells. ' 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 65%

Role of glycolysis inhibition and poly(ADP‐ribose) polymerase activation in necrotic‐like cell death caused by ascorbate/menadione‐induced oxidative stress in K562 human chronic myelogenous leukemic cells

Verrax

Vanbever

Stockis

et al. 2006

Intl Journal of Cancer

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“…Autophagy protects organisms against diverse pathologies, including infections, cancer, neurodegeneration, aging, and heart disease [198][199][200][201][202][203][204][205], and impairments in autophagolysosomal maturation are associated with Alzheimer's disease [209]. Since autophagy depends upon both cholesterol and sulfate in the lysosome, NO inhibition of autophagy is an appropriate response, as our hypothesis implies that the presence of NO is an indicator of impaired Ch-S synthesis.…”

Section: Discussionmentioning

confidence: 75%

“…The GAPDH tetramer contains 16 free thiols, including 4 active site thiols. NO inhibits the activity of GAPDH by nitrosylating one or more of its active site thiols, and this prevents them from oxidizing to sulfenic acid [198]. During glycolysis, NAD + is reduced to NADH.…”

Section: No and Autophagy Suppressionmentioning

confidence: 99%

Is Endothelial Nitric Oxide Synthase a Moonlighting Protein Whose Day Job is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease

Seneff

Lauritzen

Davidson³

et al. 2012

Entropy

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Theoretical inferences, based on biophysical, biochemical, and biosemiotic considerations, are related here to the pathogenesis of cardiovascular disease, diabetes, and other degenerative conditions. We suggest that the "daytime" job of endothelial nitric oxide synthase (eNOS), when sunlight is available, is to catalyze sulfate production. There is a striking alignment between cell types that produce either cholesterol sulfate or sulfated polysaccharides and those that contain eNOS. The signaling gas, nitric oxide, a wellknown product of eNOS, produces pathological effects not shared by hydrogen sulfide, a sulfur-based signaling gas. We propose that sulfate plays an essential role in HDL-A1 cholesterol trafficking and in sulfation of heparan sulfate proteoglycans (HSPGs), both critical to lysosomal recycling (or disposal) of cellular debris. HSPGs are also crucial in glucose metabolism, protecting against diabetes, and in maintaining blood colloidal suspension and capillary flow, through systems dependent on water-structuring properties of sulfate, an anionic kosmotrope. When sunlight exposure is insufficient, lipids accumulate in the atheroma in order to supply cholesterol and sulfate to the heart, using a OPEN ACCESSEntropy 2012, 14 2493 process that depends upon inflammation. The inevitable conclusion is that dietary sulfur and adequate sunlight can help prevent heart disease, diabetes, and other disease conditions.

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“…GAPDH has been previously shown to be inhibited in response to NO or S-nitrosothiol treatment (10,17,20,21). Here we characterized the pattern of GAPDH inhibition and distinguished between the effects of S-nitrosothiol transport and NO by treating endothelial cells with either a transportable S-nitrosothiol, CysNO, or with Sper/NO, a NO donor.…”

Section: Resultsmentioning

confidence: 96%

Differential mechanisms of inhibition of glyceraldehyde-3-phosphate dehydrogenase byS-nitrosothiols and NO in cellular and cell-free conditions

Broniowska

Hogg

2010

American Journal of Physiology-Heart and Circulatory Physiology

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Broniowska KA, Hogg N. Differential mechanisms of inhibition of glyceraldehyde-3-phosphate dehydrogenase by S-nitrosothiols and NO in cellular and cell-free conditions. Am J Physiol Heart Circ Physiol 299: H1212-H1219, 2010. First published July 30, 2010; doi:10.1152/ajpheart.00472.2010.-S-nitrosothiols are nitric oxide (NO)-derived molecules found in biological systems. They have been variously discussed as both NO reservoirs and as major actors in NO-dependent, but cGMP-independent, signal transduction. Although S-nitrosation of specific cysteine residues has been suggested to represent a novel redox-based signaling mechanism, the exact mechanisms of S-nitrosothiol formation under (patho)physiological conditions and the determinants of signaling specificity have not yet been established. Here we examined the sensitivity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to inhibition by S-nitrosocysteine (CysNO) and NO both intracellularly and in isolation. Bovine aortic endothelial cells (BAECs) and purified GAPDH preparations were treated with CysNO or NO, and enzymatic activity was monitored. Intracellular GAPDH was irreversibly inhibited upon CysNO administration, whereas treatment with NO resulted in a DTT-reversible inhibition of the enzyme. Purified GAPDH was inhibited by both CysNO and NO, but the inhibition pattern was diametrically opposite to that observed in the cells; CysNO-dependent inhibition was reversed with DTT, whereas NO-dependent inhibition was not. In the presence of GSH, NO inhibited purified GAPDH in a DTT-reversible way. Our data suggest that in response to CysNO treatment, cellular GAPDH undergoes S-nitrosation, which results in an irreversible inhibition of the enzyme under turnover conditions. In contrast, NO inhibits the enzyme via oxidative mechanisms that do not involve S-nitrosation and are reversible. In summary, our data show that GAPDH is a target for CysNO-and NO-dependent inhibition; however, these two agents inhibit the enzyme via different mechanisms both inside the cell and in isolation. Additionally, the differences observed between the cellular system and purified protein strongly imply that the intracellular environment dictates the mechanism of inhibition. nitric oxide; S-nitrosation; S-nitrosocysteine THE OBSERVATION THAT S-nitrosocysteine (CysNO) is transported into cells via amino acid transport system L and can modify intracellular protein thiols through a transnitrosation reaction, without the intermediacy of nitric oxide (NO), has provided an important tool that can be used to gain insight into the fundamental mechanisms of NO signaling (33). There is significant literature that has emphasized the role of protein S-nitrosation as the major posttranslational modification involved in cGMPindependent signaling by NO (9). Through relatively unclear mechanisms, NO is thought to S-nitrosate specific protein thiols, resulting in the initiation or the modulation of cellular signaling cascades. Some examples are the S-nitrosation of the Ras oncogene, which has been rep...

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Critical role of sulfenic acid formation of thiols in the inactivation of glyceraldehyde-3-phosphate dehydrogenase by nitric oxide

Cited by 82 publications

References 42 publications

Role of glycolysis inhibition and poly(ADP‐ribose) polymerase activation in necrotic‐like cell death caused by ascorbate/menadione‐induced oxidative stress in K562 human chronic myelogenous leukemic cells

Role of glycolysis inhibition and poly(ADP‐ribose) polymerase activation in necrotic‐like cell death caused by ascorbate/menadione‐induced oxidative stress in K562 human chronic myelogenous leukemic cells

Is Endothelial Nitric Oxide Synthase a Moonlighting Protein Whose Day Job is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease

Differential mechanisms of inhibition of glyceraldehyde-3-phosphate dehydrogenase byS-nitrosothiols and NO in cellular and cell-free conditions

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