Reactive oxygen species-mediated regulation of the Na+- H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers

S. Akram, H. F.C. Teong, L. Fliegel, S. Pervaiz, M. V. Clément

Research output: Contribution to journalArticleResearchpeer-review

Abstract

We have previously demonstrated that a slight increase in intracellular superoxide (O2•-) anion confers resistance to death stimuli. Using pharmacological and molecular approaches to manipulate intracellular O2•-, here we report that an increase in intracellular O2•- anion induces Na+/H+ exchanger 1 (NHE-1) gene promoter activity resulting in increased NHE-1 protein expression, which strongly correlates with the resistance of cells to death stimuli. In contrast, exposure to exogenous hydrogen peroxide suppressed NHE-1 promoter activity and gene expression, and increased cell sensitivity to death triggers. Furthermore, the increase in cell sensitivity to death upon downregulation of NHE-1 gene expression correlates with reduced capacity of cells to recover from an acid load, while survival upon overexpression of NHE-1 appears independent of its pump activity. These findings indicate that NHE-1 is a redox-regulated gene, and provide a novel intracellular target for the redox control of cell death sensitivity.

Original languageEnglish
Pages (from-to)628-641
Number of pages14
JournalCell Death and Differentiation
Volume13
Issue number4
DOIs
Publication statusPublished - 1 Apr 2006
Externally publishedYes

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Sodium-Hydrogen Antiporter
Oxidation-Reduction
Reactive Oxygen Species
Gene Expression
Cell Death
Superoxides
Hydrogen Peroxide
Genes
Anions
Down-Regulation
Pharmacology
Acids
Proteins

Cite this

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title = "Reactive oxygen species-mediated regulation of the Na+- H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers",
abstract = "We have previously demonstrated that a slight increase in intracellular superoxide (O2•-) anion confers resistance to death stimuli. Using pharmacological and molecular approaches to manipulate intracellular O2•-, here we report that an increase in intracellular O2•- anion induces Na+/H+ exchanger 1 (NHE-1) gene promoter activity resulting in increased NHE-1 protein expression, which strongly correlates with the resistance of cells to death stimuli. In contrast, exposure to exogenous hydrogen peroxide suppressed NHE-1 promoter activity and gene expression, and increased cell sensitivity to death triggers. Furthermore, the increase in cell sensitivity to death upon downregulation of NHE-1 gene expression correlates with reduced capacity of cells to recover from an acid load, while survival upon overexpression of NHE-1 appears independent of its pump activity. These findings indicate that NHE-1 is a redox-regulated gene, and provide a novel intracellular target for the redox control of cell death sensitivity.",
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Reactive oxygen species-mediated regulation of the Na+- H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers. / Akram, S.; Teong, H. F.C.; Fliegel, L.; Pervaiz, S.; Clément, M. V.

In: Cell Death and Differentiation, Vol. 13, No. 4, 01.04.2006, p. 628-641.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Reactive oxygen species-mediated regulation of the Na+- H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers

AU - Akram, S.

AU - Teong, H. F.C.

AU - Fliegel, L.

AU - Pervaiz, S.

AU - Clément, M. V.

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AB - We have previously demonstrated that a slight increase in intracellular superoxide (O2•-) anion confers resistance to death stimuli. Using pharmacological and molecular approaches to manipulate intracellular O2•-, here we report that an increase in intracellular O2•- anion induces Na+/H+ exchanger 1 (NHE-1) gene promoter activity resulting in increased NHE-1 protein expression, which strongly correlates with the resistance of cells to death stimuli. In contrast, exposure to exogenous hydrogen peroxide suppressed NHE-1 promoter activity and gene expression, and increased cell sensitivity to death triggers. Furthermore, the increase in cell sensitivity to death upon downregulation of NHE-1 gene expression correlates with reduced capacity of cells to recover from an acid load, while survival upon overexpression of NHE-1 appears independent of its pump activity. These findings indicate that NHE-1 is a redox-regulated gene, and provide a novel intracellular target for the redox control of cell death sensitivity.

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