Thiol-mediated redox regulation of apoptosis. Possible roles of cellular thiols other than glutathione in T cell apoptosis.
Thiol redox status modulates various aspects of cellular function. We demonstrate that oxidation of cellular sulfhydryl (SH) groups induces apoptosis. In Jurkat T cells and human PBL blasts, the fraction of apoptotic nuclei increased after treatment with an SH-specific oxidant, diamide. Analysis of DNA fragmentation and nuclear morphology also indicated that SH oxidation could induce apoptosis. In the apoptosis induced by SH oxidation, the decrease of cellular glutathione was transient and the increase of glutathione disulfide was observed only after apoptotic changes had occurred. Depletion of cellular glutathione with buthionine sulfoximine failed to induce apoptosis, despite a marked decrease of cellular glutathione, which was greater than that observed in apoptosis induced by diamide. Thus, the changes of cellular glutathione or glutathione disulfide may not be the major cause of apoptosis induced by diamide. Intracellular adult T cell leukemia-derived factor/human thioredoxin, another thiol-related antioxidant protein, was oxidized by incubation with diamide. These results suggest that thiol redox status is one of the key factors of the apoptotic pathway in which thiols other than glutathione may play even more critical roles.
Sato
N
N
Institute for Virus Research, Kyoto University, Japan.
Iwata
S
S
Nakamura
K
K
Hori
T
T
Mori
K
K
Yodoi
J
J
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016207:Cytokines; D004247:DNA / Q000032:analysis; D003958:Diamide / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D013879:Thioredoxins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016207:Cytokines; D009363:Neoplasm Proteins; D013438:Sulfhydryl Compounds; C055533:adult T cell leukemia-derived factor; D003958:Diamide; D013879:Thioredoxins; D004247:DNA; D005978:Glutathione; D019803:Glutathione Disulfide