INTRACELLULAR SIGNALING FOR SMOOTH MUSCLE CELL LOCOMOTION.
| Project/Area Number |
06836020
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
血管生物学
|
|---|
| Research Institution | NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE |
|---|
Principal Investigator |
SHIMOKADO Kentaro NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE,DIVISION OF VASCURAR BIOLOGY,CHIEF OF LABORATORY, 循環動態機能部, 室長 (30192115)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKAICHI Shigeko NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE,DEPARTMENT OF ETIOLOGY, 病因部, 室員 (00093930)
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Project Status |
Completed (Fiscal Year 1995)
|
| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Keywords | CHEMOTAXIS / TYROSINE KINASE / INHIBITORS / DNA SYNTHESIS / SRC / CSK / PHOSPHATIDYLINOSITOL 3-KINASE / phosphatidylinositol 3-kinase / Chemotaxis / 血管平滑筋 / 遊走 / 細胞周期 / 細胞骨格 / チロシンりん酸化 / 阻害剤 |
|---|
| Research Abstract |
Protein tyrosine kinase (PTK) inhibitors have been reported to inhibit proliferation of vascular smooth muscle cells (SMC). To elucidate the mode of this inhibition, the effects on the cell cycle of cultured vascular SMC of three PTK inhibitors with different modes of action (methy1 2,5-dihydroxycinnamate, genistein, and herbimycin A) were studied. Rat aortic SMC were synchronized to the G0 phase of the cell cycle, then released to proceed the cell cycle by adding PDGF,and [^3H]-thymidine incorporation into DNA was measured. The three PTK inhibitors all inhibited PDGF-induced DNA synthesis in a dosedependent fashion, with IC_<50> values of 4.7-1.4mM for methyl 2,5-dihydroxycinnamate, 6.7-1.28mM for genistein, and 0.17-0.07mM for herbimycin A.Time course studies suggested that the agents inhibited early G1 phase but not the G0-G1 transition. The lack of effect on the G0-G1 transition was also supported by the finding that the agents did not inhibit the ligand-induced autophosphorylation of PDGF receptor nor the induction of cfos mRNA at concentrations which were sufficient to inhibit DNA synthesis.PTK inhibitors inhibited progression of the S phase when they were added to SMC that had been arrested at the G1-S border with hydroxyurea. Methyl 2,5-dihydroxycinnamate also blocked the M phase when it was added to SMC cultured in the presence of 10% fetal calf serum, while genistein and herbimycin A did not inhibit the M phase under the same experimental conditions. In accordance with our previous observation, methyl 2,5-dihydroxycinnamate impaired microtubule networks and formation of the mitotic spindle during the M phase. Our findings indicated that PTK inhibitors inhibit multiple steps of the vascular SMC cell cycle.
|
Report
(3 results)
Research Products
(14 results)
