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This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/E62    most recent 00053.2007v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Dominy, J. E. Articles by Stipanuk, M. H. Search for Related Content PubMed PubMed Citation Articles by Dominy, J. E., Jr. Articles by Stipanuk, M. H.

Overexpression of cysteine dioxygenase reduces intracellular cysteine and glutathione pools in HepG2/C3A cells

Department of Nutritional Sciences, Cornell University, Ithaca, New York

Submitted 22 January 2007 ; accepted in final form 13 February 2007

Cysteine levels are carefully regulated in mammals to balance metabolic needs against the potential for cytotoxicity. It has been postulated that one of the major regulators of intracellular cysteine levels in mammals is cysteine dioxygenase (CDO). Hepatic expression of this catabolic enzyme increases dramatically in response to increased cysteine availability and may therefore be part of a homeostatic response to shunt excess toxic cysteine to more benign metabolites such as sulfate or taurine. Direct experimental evidence, however, is lacking to support the hypothesis that CDO is capable of altering steady-state intracellular cysteine levels. In this study, we expressed either the wild-type (WT) or a catalytically inactivated mutant (H86A) isoform of CDO in HepG2/C3A cells (which do not express endogenous CDO protein) and cultured them in different concentrations of extracellular cysteine. WT CDO, but not H86A CDO, was capable of reducing intracellular cysteine levels in cells incubated in physiologically relevant concentrations of cysteine. WT CDO also decreased the glutathione pool and potentiated the toxicity of CdCl₂. These results demonstrate that CDO is capable of altering intracellular cysteine levels as well as glutathione levels.

sulfur metabolism; taurine; hepatoma; liver

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				J. E. Dominy Jr, C. R. Simmons, L. L. Hirschberger, J. Hwang, R. M. Coloso, and M. H. Stipanuk Discovery and Characterization of a Second Mammalian Thiol Dioxygenase, Cysteamine Dioxygenase J. Biol. Chem., August 31, 2007; 282(35): 25189 - 25198. [Abstract] [Full Text] [PDF]