HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 12, 8759-8767, March 23, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/12/8759    most recent M610078200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tarze, A. Articles by Plateau, P. Search for Related Content PubMed PubMed Citation Articles by Tarze, A. Articles by Plateau, P. Social Bookmarking                      What's this?

Extracellular Production of Hydrogen Selenide Accounts for Thiol-assisted Toxicity of Selenite against Saccharomyces cerevisiae^*

Agathe Tarze¹², Marc Dauplais², Ioana Grigoras³, Myriam Lazard, Nguyet-Thanh Ha-Duong⁴, Frédérique Barbier, Sylvain Blanquet, and Pierre Plateau⁵

From the Laboratoire de Biochimie, UMR CNRS 7654, Département de Biologie, Ecole Polytechnique, 91128 Palaiseau Cedex and the Service Central d'Analyse, USR CNRS 59, Chemin du Canal, BP 22, 69390 Vernaison, France

Administration of selenium in humans has anticarcinogenic effects. However, the boundary between cancer-protecting and toxic levels of selenium is extremely narrow. The mechanisms of selenium toxicity need to be fully understood. In Saccharomyces cerevisiae, selenite in the millimolar range is well tolerated by cells. Here we show that the lethal dose of selenite is reduced to the micromolar range by the presence of thiols in the growth medium. Glutathione and selenite spontaneously react to produce several selenium-containing compounds (selenodiglutathione, glutathioselenol, hydrogen selenide, and elemental selenium) as well as reactive oxygen species. We studied which compounds in the reaction pathway between glutathione and sodium selenite are responsible for this toxicity. Involvement of selenodiglutathione, elemental selenium, or reactive oxygen species could be ruled out. In contrast, extracellular formation of hydrogen selenide can fully explain the exacerbation of selenite toxicity by thiols. Indeed, direct production of hydrogen selenide with D-cysteine desulfhydrase induces high mortality. Selenium uptake by S. cerevisiae is considerably enhanced in the presence of external thiols, most likely through internalization of hydrogen selenide. Finally, we discuss the possibility that selenium exerts its toxicity through consumption of intracellular reduced glutathione, thus leading to severe oxidative stress.

Received for publication, October 27, 2006 , and in revised form, January 24, 2007.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Recipient of a fellowship from the French national Programme inter-organismes "Toxicologie Nucléaire."

² Both authors contributed equally to this work.

³ Current address: Institut des Sciences du Végétal, CNRS, Avenue de la Terrasse, Bât. 23, 91198 Gif-sur-Yvette Cedex, France.

⁴ Current address: Laboratoire Interfaces, Traitements, Organisation et Dynamique des Systèmes, Université Paris VII, 1, rue Guy de la Brosse, 75005 Paris, France.

⁵ To whom correspondence should be addressed. Tel.: 33-1-69-33-41-81; Fax: 33-1-69-33-30-13; E-mail: plateau{at}bioc.polytechnique.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?