Involvement of SAPK/JNK pathway in X-ray-induced rapid cell death of human T-cell leukemia cell line MOLT-4.
We found that SAPK/JNK was phosphorylated during X-ray-induced rapid cell death of MOLT-4 cells and that acid Sphingomyelinase inhibitor D609 suppressed the rapid cell death as well as phosphorylation of SAPK/JNK. Also C2-ceramide caused phosphorylation of SAPK/JNK, followed by rapid cell death. Further we isolated X-ray-resistant radiation-hybrid clones from MOLT-4 and 50 Gy irradiated mouse FM3A cells by repeated selections with 3 Gy irradiation. One of them named Rh-1a was found resistant to X-ray- as well as C2-ceramide-induced rapid cell death. Rh-1a cells had mouse DNA but no increase in either mouse or human Bcl-2 determined by Western blotting. Accumulation of p53 after X-irradiation was similarly observed in both parental MOLT-4 and Rh-1a cells. However, contrasting to prolonged and prominent phosphorylated status of SAPK/JNK in MOLT-4 cells, Rh-1a cells exhibited short transient increase and FM3A cells showed no increase of phosphorylated status SAPK/JNK after X-irradiation. Therefore, SAPK/JNK activation is considered important in X-ray-induced rapid cell death or apoptosis of MOLT-4 cells.
Enomoto
A
A
Department of Radiation Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 113-0033, Tokyo, Japan.
Suzuki
N
N
Hirano
K
K
Matsumoto
Y
Y
Morita
A
A
Sakai
K
K
Koyama
H
H
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D016923:Cell Death / Q000528:radiation effects*; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015458:Leukemia, T-Cell / Q000532:radiotherapy*; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014965:X-Rays
D001952:Bridged-Ring Compounds; D004791:Enzyme Inhibitors; C064769:N-acetylsphingosine; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D013859:Thiocarbamates; D013871:Thiones; D016159:Tumor Suppressor Protein p53; C046498:tricyclodecane-9-yl-xanthogenate; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine