Chloride-dependent acceleration of cell cycle via modulation of Rb and cdc2 in osteoblastic cells.
In the present study, we investigated if Cl(-) regulates the proliferation of the MC3T3-E1 osteoblastic cells. The proliferation of MC3T3-E1 osteoblastic cells was diminished by lowering the extracellular Cl(-) concentration ([Cl(-)](o)) in the culture medium. The lowered in [Cl(-)](o) increased the periods of the G(0)/G(1) and the G(2)/M phases in cell cycle. We further studied the effects of [Cl(-)](o) on the key enzymes, Rb and cdc2, playing key roles in checking points of the G(0)/G(1) and the G(2)/M phases in cell cycle. The lowered in [Cl(-)](o) diminished the active forms of enzymes, Rb and cdc2. We further found that the action of lowered [Cl(-)](o) on the cell proliferation, the cell cycle, Rb and cdc2 was abolished by the presence of 2mM glutamine, but not by that of pyruvate as another Krebs cycle substrate. Taken together, these observations indicate here for the first time that Cl(-) modulates Rb and cdc2, enhancing the proliferation of the MC3T3-E1 osteoblastic cells.
Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Masahiro
M
Maki
Hiroaki
H
Miyazaki
Ken-ichi
K
Nakajima
Junko
J
Yamane
Naomi
N
Niisato
Toru
T
Morihara
Toshikazu
T
Kubo
Yoshinori
Y
Marunaka
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D002712:Chlorides / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology*; D016160:Retinoblastoma Protein / Q000378:metabolism*
D002712:Chlorides; D016160:Retinoblastoma Protein; D016203:CDC2 Protein Kinase