Activation of mitogen activated protein kinase in dolichyl phosphate-induced apoptosis in U937 cells.
Exogenous dolichyl phosphate (Dol-P) induced apoptosis in the human monoblastic leukemia cell line U937 within 4 hours. Phosphorylation of p42 mitogen-activated protein kinase (MAP kinase) increased prior to DNA fragmentation. MAP kinase activation occurred within 5 min, and the maximum response was observed at 30 min. Inhibition of tyrosine phosphorylation of MAP kinase by herbimycin A resulted in complete inhibition of DNA fragmentation and partial inhibition of cell death. These results suggested that Dol-P-induced apoptosis is mediated by the MAP kinase cascade.
Dohi
T
T
Division of Biochemistry and Nutrition, International Medical Center of Japan, Tokyo, Japan.
Yasugi
E
E
Oshima
M
M
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000032:analysis / Q000187:drug effects; D004288:Dolichol Phosphates / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D047029:Lactams, Macrocyclic; D007948:Leukemia, Monocytic, Acute; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D004273:DNA, Neoplasm; D004288:Dolichol Phosphates; D047029:Lactams, Macrocyclic; D011809:Quinones; C028306:dolichol monophosphate; D017828:Rifabutin; C020754:herbimycin; D017871:Calcium-Calmodulin-Dependent Protein Kinases