High pressure sensitizes murine erythroleukemia cells to caffeine-induced premature mitosis.
Murine erythroleukemia (MEL) cells were exposed to a high pressure of 80 MPa or aphidicolin (APH), DNA polymerase inhibitor. The effects of caffeine on cell cycle were examined using these cells. During the culture of 80 MPa-treated MEL cells at atmospheric pressure, the cells arrested in the G2 phase, and cyclin B and hyperphosphorylated p34(cdc2) were accumulated. Namely, maturation promoting factor (MPF) composed of p34(cdc2) and cyclin B was inactive. However, upon exposure to caffeine, these cells entered prematurely into mitosis by activating MPF. Caffeine-induced premature mitosis was suppressed by butyrolactone I and orthovanadate. On the other hand, APH-treated MEL cells, which were not exposed to 80 MPa, were not so sensitive to caffeine-induced premature mitosis despite cyclin B accumulation. In this case, dephosphorylation of p34(cdc2) was not induced by caffeine. Interestingly, caffeine-induced premature mitosis in the 80 MPa-treated cells was also suppressed by APH. These results suggest that the premature mitosis of 80 MPa-treated MEL cells by caffeine is induced by active MPF, and that APH-sensitive molecules such as DNA polymerase may also play an important role in the checkpoint that controls the transition from G2 to M phase.
Matsumoto
M
M
Department of Chemistry, Faculty of Science, Fukuoka University, Fukuoka, 814-0180, Japan. takeo@fukuoka-u.ac.jp
Yamaguchi
T
T
Nakazono
K
K
Fukumaki
Y
Y
Terada
S
S
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D001274:Atmospheric Pressure; D002110:Caffeine / Q000494:pharmacology*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology; D004915:Leukemia, Erythroblastic, Acute; D008938:Mitosis / Q000187:drug effects* / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D016590:Aphidicolin; D002110:Caffeine; D004259:DNA-Directed DNA Polymerase