No evidence for inhibition of human glutathione reductase by valproic acid

Nordhoff, Axel; Rh, Schirmer; Mayatepek, Ertan; Becker, Katja

doi:10.1016/0006-2952(94)90347-6

Cited by 5 publications

(6 citation statements)

References 8 publications

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“…Therefore, we cannot explain the effect of VPA by an action on GSH metabolism, notably in MRC-5 cells. In addition, Nordhoff et al (1994) recently reported that they could not detect any significant effect of VPA on glutathione reductase.…”

Section: Discussionmentioning

confidence: 99%

Sodium valproate, an anticonvulsant drug, stimulates human cytomegalovirus replication

Kuntz-Simon

Obert

1995

Journal of General Virology

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Valproic acid (VPA), a simple branched-chain fatty acid having anticonvulsant activity and used in the treatment of many forms of epilepsy, markedly stimulated human cytomegalovirus (HCMV) replication in human fibroblasts (MRC-5 cells). The maximum level of stimulation was reached when cells were treated for 24 h before infection. The enhancement of virus replication correlated with an increase in the number of immediate early (IE) and early (E) antigen-positive cells. VPA also induced expression of IE antigens after transfection of fibroblasts with a plasmid containing the entire IE1-2 region. Moreover, VPA stimulated the HCMV IE1-2 promoter/enhancer-mediated expression of fl-galactosidase in a stably transfected Jurkat T cell line. Recently, VPA was shown to inhibit glutathione reductase in human red blood cells, but an action through the glutathione metabolic pathway can be eliminated in this case, since VPA decreased the intracellular level of glutathione in Jurkat T cells but not in MRC-5 cells. The ability of VPA to stimulate HCMV replication provides an attractive model for studying the molecular mechanism of the regulation of HCMV IE1-2 gene expression.

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Section: Discussionmentioning

confidence: 99%

Sodium valproate, an anticonvulsant drug, stimulates human cytomegalovirus replication

Kuntz-Simon

Obert

1995

Journal of General Virology

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“…The high ratio of 2GSH/GSSG of about 100 is probably not different from dithiol/disulfide ratios within primordial cells that existed under a reducing atmosphere 2 billion years ago. [204] Thiol functions in proteins and coenzymes are crucial for cellular life and must be protected. In the absence of redox buffering mechanisms, atmospheric O 2 would lead to complete disappearance of intracellular thiols, and instead sulfates and sulfinates would become the predominant form of sulfur compounds in the presence of dioxygen.…”

Section: Outlook On Drug Developmentmentioning

confidence: 99%

“…In the absence of redox buffering mechanisms, atmospheric O 2 would lead to complete disappearance of intracellular thiols, and instead sulfates and sulfinates would become the predominant form of sulfur compounds in the presence of dioxygen. [54,204] Redox Environment. Schafer and Buettner [205] define the redox environment in a cell compartment as [Eq.…”

Section: Outlook On Drug Developmentmentioning

confidence: 99%

Dithiol Proteins as Guardians of the Intracellular Redox Milieu in Parasites: Old and New Drug Targets in Trypanosomes and Malaria‐Causing Plasmodia

2005

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Parasitic diseases such as sleeping sickness, Chagas' heart disease, and malaria are major health problems in poverty-stricken areas. Antiparasitic drugs that are not only active but also affordable and readily available are urgently required. One approach to finding new drugs and rediscovering old ones is based on enzyme inhibitors that paralyze antioxidant systems in the pathogens. These antioxidant ensembles are essential to the parasites as they are attacked in the human host by strong oxidants such as peroxynitrite, hypochlorite, and H2O2. The pathogen-protecting system consists of some 20 thiol and dithiol proteins, which buffer the intraparasitic redox milieu at a potential of -250 mV. In trypanosomes and leishmania the network is centered around the unique dithiol trypanothione (N1,N8-bis(glutathionyl)spermidine). In contrast, malaria parasites have a more conservative dual antioxidative system based on glutathione and thioredoxin. Inhibitors of antioxidant enzymes such as trypanothione reductase are, indeed, parasiticidal but they can also delay or prevent resistance against a number of other antiparasitic drugs.

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“…VPA depressed the GSH level in Jurkat T cells and in U937 cells (from which the U1 cell line was derived) at concentrations which stimulated LTR-driven gene expression or viral replication (Simon et aI., 1994). However, the GSH decrease observed in Jurkat T cells and U937 is perhaps not the consequence of the GSH reductase inhibition since Nordhoff et al (1994) reported that they could not reproduce the previously described effects of VPA on GSH reductase activity.…”

Section: Discussionmentioning

confidence: 73%

Sodium Valproate, an Anticonvulsant Drug, Stimulates Human Immunodeficiency Virus Type 1 Replication Independently of Glutathione Levels

Moog

Kuntz-Simon²,

Caussin‐Schwemling

et al. 1996

Journal of General Virology

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No evidence for inhibition of human glutathione reductase by valproic acid

Cited by 5 publications

References 8 publications

Sodium valproate, an anticonvulsant drug, stimulates human cytomegalovirus replication

Sodium valproate, an anticonvulsant drug, stimulates human cytomegalovirus replication

Dithiol Proteins as Guardians of the Intracellular Redox Milieu in Parasites: Old and New Drug Targets in Trypanosomes and Malaria‐Causing Plasmodia

Sodium Valproate, an Anticonvulsant Drug, Stimulates Human Immunodeficiency Virus Type 1 Replication Independently of Glutathione Levels

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