Staurosporine-induced thymocyte apoptosis is inhibited by herbimycin A, a specific inhibitor of protein tyrosine kinase.
When mouse thymocytes were incubated with staurosporine at low doses (1-100 nM), increased tyrosine phosphorylation of proteins with a molecular weight of 31-34 kD in the detergent-soluble fraction was observed, together with an increase in internucleosomal DNA fragmentation. Incubation with staurosporine for 6 h was enough to trigger and progress of apoptosis. Herbimycin A, a specific inhibitor of protein tyrosine kinases, and cycloheximide, an inhibitor of protein synthesis, reduced the amount of the phosphotyrosine proteins, this being followed by the inhibition of DNA fragmentation and cell death, suggesting a close relationship between protein tyrosine phosphorylation and the induction of apoptosis by staurosporine.
Azuma
Y
Y
Department of Biochemistry, Tokyo Dental College, Chiba, Japan.
Onishi
Y
Y
Hirata
C
C
Tanimoto
Y
Y
Yamada
T
T
Kizaki
H
H
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones; D002478:Cells, Cultured; D004336:Drug Antagonism; D047029:Lactams, Macrocyclic; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D019311:Staurosporine; D013601:T-Lymphocytes / Q000473:pathology*
D000470:Alkaloids; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine