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 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.
Bae
M A
MA
Department of Microbiology, College of Natural Sciences, Kyungpook National University, Taegu, Korea.
Kang
H S
HS
Rue
S W
SW
Seu
J H
JH
Kim
Y H
YH
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D007769:Lactams; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007769:Lactams; D008562:Membrane Glycoproteins; D011758:Pyrroles; C112446:aburatubolactam C; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases