Mammalian Small Stress Proteins Protect against Oxidative Stress through Their Ability to Increase Glucose-6-phosphate Dehydrogenase Activity and by Maintaining Optimal Cellular Detoxifying Machinery

doi:10.1006/excr.1998.4347

Experimental Cell Research

Volume 247, Issue 1, 25 February 1999, Pages 61-78

https://doi.org/10.1006/excr.1998.4347 Get rights and content

Abstract

The protective activity of small stress proteins (sHsp) against H₂O₂-mediated cell death in the highly sensitive murine L929 fibroblast has been analyzed. We report here that the human Hsp27- and murine Hsp25-mediated rise in glutathione (GSH) levels as well as the maintenance of this redox modulator in its reduced form was directly responsible for the protection observed at the level of cell morphology and mitochondrial membrane potential. sHsp expression also buffered the increase in protein oxidation following H₂O₂treatment and protected several key enzymes against inactivation. In this case, however, the protection necessitated both an increase in GSH and the presence of sHspper sesince the pattern of protection against protein oxidation mediated by a simple GSH increase was different from that induced by sHsp expression. Among the enzymes analyzed, we noticed that sHsp significantly increased glucose-6-phosphate dehydrogenase (G6PD) activity and to a lesser extent glutathione reductase and glutathione transferase activities. Moreover, an increased GSH level was observed in G6PD-overexpressing L929 cell clones. Taken together our results suggest that sHsp protect against oxidative stress through a G6PD-dependent ability to increase and uphold GSH in its reduced form and by using this redox modulator as an essential parameter of theirin vivochaperone activity against oxidized proteins.

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^☆: T. B. Society

¹: X.P. and F.S. contributed equally to this work.

²: To whom correspondence and reprint requests should be addressed. Fax: +33 (0) 472440555. E-mail:[email protected].

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Regular ArticleMammalian Small Stress Proteins Protect against Oxidative Stress through Their Ability to Increase Glucose-6-phosphate Dehydrogenase Activity and by Maintaining Optimal Cellular Detoxifying Machinery☆

Abstract

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Arch. Biochem. Biophys.

Methods Enzymol.

Int. J. Radiat. Oncol. Biol. Phys.

Oxidative stress: The paradox of aerobic life

Free Radicals and Oxidative Stress: Environment, Drugs and Food Additives

Protein oxidation and aging

Science

The role of oxygen radicals in human disease, with particular reference to the vascular system

Haemostasis

Thioctic acid protects against ischemia–reperfusion injury in the isolated perfused Langendorff heart

Free Radical Res. Commun.

Glutathione

Annu. Rev. Biochem.

Targeted disruption of the housekeeping gene encoding glucose 6-phosphate dehydrogenase (G6PD): G6PD is dispensable for pentose synthesis but essential for defense against oxidative stress

EMBO J.

Glutathione depletion is an early and calcium elevation is a late event of thymocyte apoptosis

J. Immunol.

Regular Article
Mammalian Small Stress Proteins Protect against Oxidative Stress through Their Ability to Increase Glucose-6-phosphate Dehydrogenase Activity and by Maintaining Optimal Cellular Detoxifying Machinery☆