ENHANCED EXPRESSION OF FAS LIGAND IS ASSOCIATED WITH ABURATUBOLACTAM-C INDUCED APOPTOSIS IN HUMAN JURKAT T-CELLS

The mechanism for apoptosis induced by aburatubolactam C was investiga ted in human Jurkat T cells. When the cells were treated with 3 mu g/m l of aburatubolactam C, apoptotic DNA fragmentation was first detectab le in 3 hr and then increased time-dependently in accordance with upre gulation in the protein level of Fas ligand (FasL). Both the DNA fragm entation and upregulation of FasL expression reached a maximal level i n 7-8 hr, at which time a significant increase in the tyrosine phospho rylation of multiple cellular proteins was detected, suggesting that t he enhanced tyrosine phosphorylation of cellular proteins may result f rom activation of Fas-mediated death signaling. However, these aburatu bolactam C-induced cellular changes and accompanied apoptosis were com pletely blocked in the presence of genistein, a known protein tyrosine kinase inhibitor. These results indicate that upregulation of FasL ex pression dictated by protein tyrosine kinase activation and subsequent mediation of Fas death signaling account for aburatubolactam C-induce d apoptosis in Jurkat T cells. (C) 1998 Academic Press.