| Project/Area Number |
09470007
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKUWA Noriko The University of Tokyo Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (70150290)
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| Co-Investigator(Kenkyū-buntansha) |
TAKUWA Yoh Kanazawa University School of Medicine, Professor, 医学部・生理学第一講座, 教授 (60171592)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 1998: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1997: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | vascular / smooth muscle / mechanical stretch / ATP / P_0 purinoceptor / signal transduction / gene expression / JNK / P2受容体 |
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| Research Abstract |
Mechanical strain has been implicated in phenotypic changes, including alteration of gene expression in vascular smooth muscle cells ; however, the molecular basis for mechanotransduction leading to nuclear gene expression is largely unknown. By using a FLEXERCELL^R strain unit, we found that cyclic stretching of vascular smooth muscle cells dramatically activates Jun N-terminal kinase(JNK)/stress-activated protein kinase(SAPK)through an autocrine mechanism. Stretch causes time-and strength-dependent rise of the ATP concentration in media. The stretch-induced activation of JNK/SAPK is attenuated by the addition of hexokinase or apyrase that scavenge ATP in media. Both the P_2 receptor antagonist and the A_1 subtype-selective P_1 receptor antagonist partially inhibit stretch-induced activation of JNK/SAPK.The conditioned medium from stretched cells contains an activity to stimulate JNK/SAPK.The JNK-stimulating activity in the conditioned medium from stretched cells is attenuated by the addition of apyrase or P_1 and P_2 receptor antagonists. The addition of exogenous ATP or adenosine induces dose-dependent activation of JNK/SAPK.These results indicate that stretch activates JNK/SAPK in vascular smooth muscle cells through mechanisms involving autocrine stimulation of purinoceptors by ATP and its hydrolyzed product adenosine.
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