Differential dependence on cysteine from transsulfuration versus transport during T cell activation.
The synthesis of glutathione, a major cellular antioxidant with a critical role in T cell proliferation, is limited by cysteine. In this study, we evaluated the contributions of the x(C)(-) cystine transporter and the transsulfuration pathway to cysteine provision for glutathione synthesis and antioxidant defense in naïve versus activated T cells and in the immortalized T lymphocyte cell line, Jurkat. We show that the x(C)(-) transporter, although absent in naïve T cells, is induced after activation, releasing T cells from their cysteine dependence on antigen-presenting cells. We also demonstrate the existence of an intact transsulfuration pathway in naïve and activated T cells and in Jurkat cells. The flux through the transsulfuration pathway increases in primary but not in transformed T cells in response to oxidative challenge by peroxide. Inhibition of the transsulfuration pathway in both primary and transformed T cells decreases cell viability under oxidative-stress conditions.
Garg
Sanjay K
SK
Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, 48109, USA.
Yan
Zhonghua
Z
Vitvitsky
Victor
V
Banerjee
Ruma
R
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010545:Peroxides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
D010545:Peroxides; D005978:Glutathione; D003545:Cysteine