Overcoming the blockade at the upstream of caspase cascade in Fas-resistant HTLV-I-infected T cells by cycloheximide |
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Authors: | Kongphanich Aurus Hieda Michinari Kurokawa Kenji Murata Takashi Kobayashi Nobuyuki |
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Affiliation: | Laboratory of Molecular Biology of Diseases, School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bnkyo-machi, Nagasaki 852-8521, Japan. |
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Abstract: | 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. |
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Keywords: | HTLV-I Fas/APO-1/CD95 Resistance Fas clustering Cycloheximide Caspase-8 |
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