The regulation of glutathione peroxidase gene expression by oxygen tension in cultured human cardiomyocytes

Cowan, Douglas B.; Weisel, Richard D.; Williams, Wendy; Mickle, Donald A.G.

doi:10.1016/0022-2828(92)93196-q

Cited by 57 publications

(16 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16,1996 REDOX REGULATION OF ZINC FINGERSoligonucleotides containing both high-and low-affinity Sp-1 sites, Egr-1, and NF-B consensus sequences were compared (Fig. 1b).…”

Section: Resultsmentioning

confidence: 99%

“…Hypoxic and hyperoxic stresses can activate or repress the transcription of certain genes by pathways that probably involve protein kinases (5,16,18,24,28,52,68,70,82,84). The response to severe oxidative stress may involve an additional effect in which redox-sensitive factors can be directly activated or inactivated through the oxidation of sulfhydryl residues.…”

mentioning

confidence: 99%

“…1 legend. VOL. 16,1996 REDOX REGULATION OF ZINC FINGERS 1039 show representative blots and quantitation, respectively, of reverse transcription QPCR-amplified CAT mRNA. Following an increase in the CAT message transcribed from pSP-1-CAT after 24 h of exposure to BSO, there was a progressive decline of CAT transcripts in cells transfected with either pSp-1-CAT or pSVSp-1-CAT after the cultures were exposed to 200 M diamide.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Physical and Functional Sensitivity of Zinc Finger Transcription Factors to Redox Change

Bishopric

Discher

et al. 1996

Molecular and Cellular Biology

189

136

View full text Add to dashboard Cite

Redox regulation of DNA-binding proteins through the reversible oxidation of key cysteine sulfhydryl groups has been demonstrated to occur in vitro for a range of transcription factors. The direct redox regulation of DNA binding has not been described in vivo, possibly because most protein thiol groups are strongly buffered against oxidation by the highly reduced intracellular environment mediated by glutathione, thioredoxin, and associated pathways. For this reason, only accessible protein thiol groups with high thiol-disulfide oxidation potentials are likely to be responsive to intracellular redox changes. In this article, we demonstrate that zinc finger DNA-binding proteins, in particular members of the Sp-1 family, appear to contain such redox-sensitive -SH groups. These proteins displayed a higher sensitivity to redox regulation than other redox-responsive factors both in vitro and in vivo. This effect was reflected in the hyperoxidative repression of transcription from promoters with essential Sp-1 binding sites, including the simian virus 40 early region, glycolytic enzyme, and dihydrofolate reductase genes. Promoter analyses implicated the Sp-1 sites in this repression. Non-Sp-1-dependent redox-regulated genes including metallothionein and heme oxygenase were induced by the same hyperoxic stress. The studies demonstrate that cellular redox changes can directly regulate gene expression in vivo by determining the level of occupancy of strategically positioned GC-binding sites.There is compelling evidence for both direct and indirect pathways for the regulation of gene expression by changes in cellular redox state. Hypoxic and hyperoxic stresses can activate or repress the transcription of certain genes by pathways that probably involve protein kinases (5,16,18,24,28,52,68,70,82,84). The response to severe oxidative stress may involve an additional effect in which redox-sensitive factors can be directly activated or inactivated through the oxidation of sulfhydryl residues. The binding of factors AP-1, Sp-1, Egr-1, NF-B, v-rel, c-myb, E2, IRE-BP, p53, and USF to nucleic acid is reduced or lost when critical cysteine residues are oxidized or alkylated (1, 3, 4, 33-35, 37, 48, 53, 60, 66, 78, 89). HoxB5, a member of the mammalian homeodomain gene family, is an example of a factor that is activated by oxidation (30). In the case of AP-1, a cellular DNA-repair protein that may regulate the redox equilibrium has been described previously (90). Oxidative inactivation of USF has been shown to correlate directly with transcriptional activity in an in vitro assay (60). It has been proposed that the reactive cysteines may constitute redox-sulfhydryl switches which directly regulate gene expression (35,60). In support of this, factor Sp-1 in rat liver appears to become progressively oxidized during aging, resulting in the reversible loss of binding activity by an in vitro assay (3). To date, there have been no reports to demonstrate that oxidizing agents or redox stresses can directly mediate transcription factor bindi...

show abstract

“…16,1996 REDOX REGULATION OF ZINC FINGERSoligonucleotides containing both high-and low-affinity Sp-1 sites, Egr-1, and NF-B consensus sequences were compared (Fig. 1b).…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Physical and Functional Sensitivity of Zinc Finger Transcription Factors to Redox Change

Bishopric

Discher

et al. 1996

Molecular and Cellular Biology

189

136

View full text Add to dashboard Cite

show abstract

“…The expression of the GPX gene, hgpx1, occurs in a wide range of tissues controlled by development, hormones and oxygen tension. In the myocardium, GPX activity induced by oxygen tension was found to be proportional to the mRNA levels, suggesting a transcriptional mechanism [128] . GPX promoter contains both NFκB and AP-1 binding sites.…”

Section: Exercise Activation Of Redox Signaling Pathwaysmentioning

confidence: 96%

Hormesis and Exercise: How the Cell Copes with Oxidative Stress

Radák

Goto

2008

American J. of Pharmacology and Toxicology

View full text Add to dashboard Cite

Contraction-induced production of reactive oxygen and nitrogen species has been shown to cause oxidative stress to skeletal muscle, heart and other organs. As an adaptive response, muscle antioxidant defense systems are upregulated in response to exercise to restore intracellular prooxidantantioxidant homeostasis. Thus, both young and old animals and humans involved in regular exercise have shown reduced oxidative damage during acute physical exertion at accustomed or excessive intensity, or under oxidative challenges otherwise deemed detrimental. The current article provides a brief review of this exercise-induced hormesis with the emphasis on the role of redox sensitive signal transduction pathways (mainly nuclear factor κB and mitogen-activated protein kinase) that can activate the gene expression of antioxidant enzymes and proteins. Molecular mechanisms and gene targets for these signaling pathways, as well as the biological significance of the adaptations, are discussed.

show abstract

“…Reductive or oxidative stresses can modulate the transcription of certain genes by pathways that probably involve protein kinases [100][101][102][103]. Additionally, the cellular response to severe oxidative conditions may affect, through the oxidation or alkylation of thiol residues, the binding mechanisms of nucleic acid regulatory factors, which can be directly activated or inactivated.…”

Section: Intracellular Znmentioning

confidence: 99%

Redox Sensitivity of Tyrosine Hydroxylase Activity and Expression in Dopaminergic Dysfunction

Giovanni

Pessia²,

Maio³

2012

CNSNDDT

View full text Add to dashboard Cite

Oxidant molecules generated during neuronal metabolism appear to play a significant role in the processes of aging and neurodegeneration. Increasing experimental evidence suggests the noteworthy relevance of the intracellular reduction-oxidation (redox) balance for the dopaminergic (DA-ergic) neurons of the substantia nigra pars compacta. These cells possess a distinct physiology intrinsically associated with elevated reactive oxygen species production, conferring on them a high vulnerability to free radical damage, one of the major causes of selective DA-ergic neuron dysfunction and degeneration related to neurological disorders such as Parkinson's disease. Tyrosine hydroxylase (tyrosine 3-monooxygenase; E.C. 1.14.16.2; TH) activity represents the rate-limiting biochemical event in DA synthesis. TH activity, metabolism and expression are finely tuned by several regulatory systems in order to maintain a crucial physiological condition in which DA synthesis is closely coupled to its secretion. Alterations of these regulatory systems of TH functions have indeed been thought to be key events in the DA-ergic degeneration. TH has seven cysteine residues presenting thiols. Depending on the oxido-reductive (redox) status of the cellular environment, thiols exist either in the reduced form of free thiols or oxidized to disulfides. The formation of disulfides in proteins exerts critical regulatory functions both in physiological and in pathological conditions when oxidative stress is sustained. Several reports have recently shown that redox state changes of thiol residues, as consequence of an oxidative injury, can directly or indirectly affect the TH activity, metabolism and expression.The major focus of this review, therefore, is to report recent evidence on the redox modulation of TH activity and expression, and to provide an overview of a cellular phenomenon that might represent a target for new therapeutic strategies against the DA-ergic neurodegenerative disorders.

show abstract

The regulation of glutathione peroxidase gene expression by oxygen tension in cultured human cardiomyocytes

Cited by 57 publications

References 27 publications

Physical and Functional Sensitivity of Zinc Finger Transcription Factors to Redox Change

Physical and Functional Sensitivity of Zinc Finger Transcription Factors to Redox Change

Hormesis and Exercise: How the Cell Copes with Oxidative Stress

Redox Sensitivity of Tyrosine Hydroxylase Activity and Expression in Dopaminergic Dysfunction

Contact Info

Product

Resources

About