Overcoming the blockade at the upstream of caspase cascade in Fas-resistant HTLV-I-infected T cells by cycloheximide.
In spite of carrying large amount of Fas death receptor on the cell surface, Human T cell lymphotropic virus type-I (HTLV-I)-infected T cell lines are resistant to Fas-mediated cytotoxicity. We investigated the mechanism(s) of HTLV-I-induced Fas resistance. Western blotting and enzymatic activity analyses revealed that the Fas-elicited apoptotic signal in HTLV-I-infected T cells was intervened at the level(s) prior to the activation of caspase-8. Upon stimulation, the clustering of Fas receptors scarcely occurred in HTLV-I-infected cells. Cycloheximide treatment converted the resistant cells to sensitive cells; the presence of short-lived anti-apoptotic molecule(s) that can block the caspase-8 activation within HTLV-I-infected T cells is suggested.
Kongphanich
Aurus
A
Laboratory of Molecular Biology of Diseases, School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bnkyo-machi, Nagasaki 852-8521, Japan.
Hieda
Michinari
M
Kurokawa
Kenji
K
Murata
Takashi
T
Kobayashi
Nobuyuki
N
D017209:Apoptosis / Q000187:drug effects; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology*; D015490:HTLV-I Infections / Q000378:metabolism* / Q000473:pathology*; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects*; D006801:Humans; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D019014:fas Receptor / Q000378:metabolism*
D011500:Protein Synthesis Inhibitors; D019014:fas Receptor; D003513:Cycloheximide; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases