Enhanced expression of Fas ligand is associated with aburatubolactam C-induced apoptosis in human Jurkat T cells

Abstract

The mechanism for apoptosis induced by aburatubolactam C was investigated in human Jurkat T cells. When the cells were treated with 3 micrograms/ml of aburatubolactam C, apoptotic DNA fragmentation was first detectable in 3 hr and then increased time-dependently in accordance with upregulation in the protein level of Fas ligand (FasL). Both the DNA fragmentation and upregulation of FasL expression reached a maximal level in 7-8 hr, at which time a significant increase in the tyrosine phosphorylation of multiple cellular proteins was detected, suggesting that the enhanced tyrosine phosphorylation of cellular proteins may result from activation of Fas-mediated death signaling. However, these aburatubolactam C-induced cellular changes and accompanied apoptosis were completely blocked in the presence of genistein, a known protein tyrosine kinase inhibitor. These results indicate that upregulation of FasL expression dictated by protein tyrosine kinase activation and subsequent mediation of Fas death signaling account for aburatubolactam C-induced apoptosis in Jurkat T cells.