Protein tyrosine kinase p56lck-deficiency confers hypersusceptibility to ρ-fluorophenylalanine (pFPhe)-induced apoptosis by augmenting mitochondrial apoptotic pathway in human Jurkat T cells
| Autor: | Do Youn Jun, Hae Sun Park, Cho Rong Han, Young Ho Kim |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Drug Resistance
Biophysics Apoptosis Cysteine Proteinase Inhibitors Mitochondrion Biology Biochemistry Mitochondrial apoptosis-induced channel Jurkat cells Jurkat Cells Humans Kinase activity Molecular Biology Phospholipase C gamma Cytochromes c p-Fluorophenylalanine Cell Biology Caspase Inhibitors Molecular biology Mitochondria Cell biology Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Caspases DNA fragmentation Oligopeptides Tyrosine kinase Phenylalanine analog |
| Zdroj: | Biochemical and Biophysical Research Communications. 377:280-285 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2008.09.126 |
| Popis: | Phenylalanine analog, rho-fluorophenylalanine (pFPhe)-mediated cytotoxicity and several apoptotic events including mitochondrial cytochrome c release, activation of caspase-9, -3, and -8, Bid cleavage, degradation of PARP and PLCgamma-1, and DNA fragmentation were more significant in p56(lck)-deficient Jurkat T cells (JCaM1.6) than in wild-type Jurkat T cells (E6.1). The susceptibility of JCaM1.6 toward apoptogenic activity of pFPhe decreased after acquisition of p56(lck) by transfection. The p56(lck) kinase activity increased 1.6-fold at 15-30 min after pFPhe treatment. The pan-caspase inhibitor (z-VAD-fmk) completely blocked the pFPhe-mediated apoptotic changes except caspase-9 activation. The caspase-8 inhibitor (z-IETD-fmk), which failed to influence pFPhe-induced caspase-9 activation, completely blocked caspase-8 activation and PLCgamma-1 degradation with a marked reduction in caspase-3 activation and PARP degradation, indicating pFPhe-induced caspase-8 activation as a downstream event of mitochondria-dependent activation of caspase-9. These results indicate that the deficiency of p56(lck) augments pFPhe-induced mitochondrial cytochrome c release and resultant apoptotic cell death in Jurkat T cells. |
| Databáze: | OpenAIRE |
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