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J. Biol. Chem., Vol. 282, Issue 28, 20416-20424, July 13, 2007

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Glutathione Is Recruited into the Nucleus in Early Phases of Cell Proliferation^*

From the Department of Physiology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain

We have studied the possible correlation between nuclear glutathione distribution and the progression of the cell cycle. The former was studied by confocal microscopy using 5-chloromethyl fluorescein diacetate and the latter by flow cytometry and protein expression of Id2 and p107. In proliferating cells, when 41% of them were in the S+G₂/M phase of the cell cycle GSH was located mainly in the nucleus. When cells reached confluence (G₀/G₁) GSH was localized in the cytoplasm with a perinuclear distribution. The nucleus/cytoplasm fluorescence ratio for GSH reached a maximal mean value of 4.2 ± 0.8 at 6 h after cell plating. A ratio higher than 2 was maintained during exponential cell growth. In the G₀/G₁ phase of the cell cycle, the nucleus/cytoplasm GSH ratio decreased to values close to 1. We report here that cells concentrate GSH in the nucleus in the early phases of cell growth, when most of the cells are in an active division phase, and that GSH redistributes uniformly between the nucleus and the cytoplasm when cells reach confluence.

Received for publication, October 11, 2006 , and in revised form, March 27, 2007.

^* This work was supported by Grants SAF2002/00885 and BFU2005-00230/BFI from the "Comisión Interministerial de Ciencia y Tecnología" and GV2004-B-169 and ACOMP06/230 from the "Generalitat Valenciana" (to F. V. P.); SAF 2004-03755 (to J. V.); and Red de Centros de Metabolismo y Nutricíon (RCMN c03/08), Madrid, Spain ("Centro de Investigacíon Biomedica en Red" for rare diseases). 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 Past recipient of a fellowship from Agencia Española de Cooperación Internacional del Ministerio de Asuntos Exteriores de España and current recipient of the "V SEGLES" fellowship from the University of Valencia.

² Present address: Universidad Católica de Valencia, 46003 Valencia, Spain.

³ To whom correspondence should be addressed: Dept. de Fisiología, Facultad de Medicina, University of Valencia, Ciberer, Av. Blasco Ibáñez 17, 46010 Valencia, Spain. Tel.: 34963864641; Fax: 34963864642; E-mail: pallardo{at}uv.es.

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