Adult T cell leukemia (ATL)-derived factor/human thioredoxin prevents apoptosis of lymphoid cells induced by L-cystine and glutathione depletion: possible involvement of thiol-mediated redox regulation in apoptosis caused by pro-oxidant state.

Abstract

Thiol compounds, such as L-cysteine and glutathione (GSH), play crucial roles in the regulation of lymphocyte proliferation. In this study, we analyzed the effect of L-cystine and GSH depletion on lymphocyte survival and investigated the regulatory roles of adult T cell leukemia (ATL)-derived factor (ADF)/human thioredoxin (hTRX) in relation to these low m.w. thiols. MT-1, MT-2, and Jurkat cells underwent apoptosis when cultured in the L-cystine- and GSH-free medium within 18 to 24 h. Dichlorofluorescin oxidation assay indicated that the apoptosis in MT-1 and MT-2 cells was preceded by an increase in the level of intracellular hydrogen peroxide (H2O2). The addition of catalase and recombinant ADF/hTRX (rADF) partially blocked the apoptosis in a dose-dependent manner. rADF has been also shown to enhance the internalization of L-cystine into MT-2 cells in a dose-dependent manner, whereas oxidized rADF or mutated rADF that has no insulin-reducing activity failed to do so. Furthermore, culture in the L-cystine- and GSH-free medium lowered the cellular GSH content of PHA blasts, which was restored dose-dependently by rADF. These data suggest that the inability to neutralize oxidative stress results in the apoptosis of lymphoid cells under L-cystine- and GSH-depleted conditions. The protective effects of rADF may be explained by direct scavenging action on H2O2 (catalase-like activity) or by indirect neutralizing effects on the pro-oxidant status through enhancing the L-cystine internalization and elevating the intracellular GSH content.

• Authors: S Iwata, T Hori, N Sato, K Hirota, T Sasada, A Mitsui, T Hirakawa, J Yodoi
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 158 Issue 7 Pg. 3108-17 (Apr 01 1997) ISSN: 0022-1767 [Print] United States
• PMID: 9120263 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media
• Cytokines
• Neoplasm Proteins
• Oxidants
• Recombinant Proteins
• Sulfhydryl Compounds
• adult T cell leukemia-derived factor
• Cystine
• Thioredoxins
• Hydrogen Peroxide
• Catalase
• Glutathione

Topics

• Apoptosis (drug effects)
• Catalase (pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Culture Media
• Cystine (deficiency, pharmacology)
• Cytokines (genetics, pharmacology)
• Glutathione (deficiency, pharmacology)
• Humans
• Hydrogen Peroxide (metabolism)
• Lymphocytes (drug effects, metabolism)
• Molecular Weight
• Neoplasm Proteins (genetics, pharmacology)
• Oxidants (pharmacology)
• Oxidation-Reduction
• Recombinant Proteins (pharmacology)
• Sulfhydryl Compounds (metabolism, pharmacology)
• Thioredoxins (pharmacology)