AI Article Synopsis
- The study investigates how rho-fluorophenylalanine (pFPhe) causes cell death through apoptosis in Jurkat T cells, with notable effects observed in cells lacking the p56(lck) protein.
- In p56(lck)-deficient Jurkat T cells, there was a significant increase in apoptotic markers, like cytochrome c release and caspase activation, compared to wild-type Jurkat T cells.
- Transfecting the deficient cells with p56(lck) reduced their susceptibility to pFPhe, demonstrating that p56(lck) plays a protective role against pFPhe-induced apoptosis.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.bbrc.2008.09.126 | DOI Listing |
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