Regulatory mechanisms of cytosolic ion transients during cell cycle progression in vascular endothelial and smooth muscle cells

血管内皮细胞和平滑肌细胞细胞周期进展过程中胞质离子瞬变的调节机制

• 批准号: 08457211
• 负责人: KOBAYASHI Sei
• 金额: $ 2.43万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457211/
• 关键词: Cell Cycle; Cell Proliferation; Blood Vessel; Vasocontraction; Vasorelaxation; Calcium Ion; Smooth Muscle Cells; Vasoactive Substances; Culcium Ion; 細胞増殖; 細胞質Ca^<2+>濃度; 血管平滑筋; 血小板由来増殖因子; 細胞周期; 細胞質カルシウムイオン濃度; 血管平滑筋細胞; カルシウムイオンチャネル; 細胞増殖因子

The following results were obtained :1. CELL PROLIFERATION OF VASCULAR SMOOTH MUSCLE CELLS AND ITS RELATION TO THE CELLULAR FUNCTION.I developed the method to determine both the phase of the cell cycIe and cell function of the same single-cell of vascular smooth muscle cells (VSMCs) in primary culture. It was found that : (1) the expression of types of Ca^<2+> channels changes with the cell cycle ; (2) the activation of P2u receptor stimulates the cell cycle progression from the G1 to the S/M phases, but not from the G0 to G1 phase, whereas it elevates cytosolic Ca^<2+> concentration ([Ca^<2+>] i) in the VSMCs at the G0 and C1 phases equally ; and (3) Ca^<2+> channel blockers differently affect Ca^<2+> transients and cell cycle progression in VSMCs.2. VASCULAR CONTRACTION.(1) Differential mechanisms ([Ca^<2+>]i-force relation, Ca^<2+> sensitivity of contractile apparatus, and mRNA expression) of vasorelaxation by vasodilators were elucidated. (2) It was found that resting load regulates [Ca^<2+>] i-force relation of the contraction of vascular smooth muscle. (3) It was found that Rho-kinase induces myosin light chain phosphorylation and Ca^<2+>-independent contraction, which is independent of the Ca^<2+>- calmodulin-MLCK pathway. (4) Bradykinin was shown to elevate [Ca^<2+>] i and Ca^<2+> sensitivity of contractile apparatus, as mediated by the activation of the B2 receptor and G-proteins. (5) It was demonstrated that tyrosine kinase Inhibitor markedly suppressed the development of coronary lesions in pig in vivo. (6) Down-regulation of endotihelin B receptors was observed in autogenous saphenous veins grafted into the arterial circulation. (7) It was suggested that endothelins may be autocrine and/or paracrine transmitters 'to regulate the contraction of airway smooth muscle.

获得了以下结果：1.血管平滑肌细胞的增殖及其与细胞功能的关系我建立了一种方法来测定原代培养的同一单个血管平滑肌细胞（VSMCs）的细胞周期时相和细胞功能。结果发现：（1）Ca^<2+>通道类型的表达随细胞周期的变化而变化;（2）P2 u受体的激活可促进细胞周期由G1期向S/M期的进程，但不能促进细胞由G 0期向G1期的进程，但可使胞浆Ca^<2+>浓度升高（3）Ca^<2 +>通道阻断剂对VSMC中Ca^<2 +>瞬变和细胞周期进程的影响不同。血管扩张。(1)阐明了血管舒张剂舒张血管的不同机制（[Ca^<2+>] i-力关系、收缩器的Ca^<2+>敏感性和mRNA表达）。(2)发现静息负荷调节血管平滑肌收缩的[Ca^<2+>] i-力关系。(3)发现Rho激酶诱导肌球蛋白轻链磷酸化和Ca^<2+>非依赖性收缩，其不依赖于Ca^<2+>-钙调蛋白-MLCK途径。(4)缓激肽可通过激活B2受体和G蛋白介导升高收缩器官的[Ca^2+] i和Ca^2+敏感性。(5)结果表明，酪氨酸激酶抑制剂对猪冠状动脉病变有明显的抑制作用。(6)内皮素B受体的下调，观察到自体隐静脉移植到动脉循环。(7)提示内皮素可能通过自分泌和/或旁分泌途径调节气道平滑肌的收缩。

项目成果

Sakihara, C.: "Direct inhibitory effect of chlorpromazine on smooth muscle of the porcine pulmonary artery." Anesthesiology. 85. 616-625 (1996)

Sakihara, C.：“氯丙嗪对猪肺动脉平滑肌的直接抑制作用。”

Kawasaki, J.: "The mechanisms of the relaxation induced by vasoactive intestinal peptide in the porcine coronary artery." Br.J.Pharmacol.121. 977-985 (1997)

Kawasaki, J.：“猪冠状动脉中血管活性肠肽诱导的舒张机制。”

Eguchi, D.: "Down-regulation of endothelin B receptors in autogenous saphenous veins grafted into the arterial circulation." Cardiovas.Res.35. 360-367 (1997)

Eguchi, D.：“移植到动脉循环的自体隐静脉中内皮素 B 受体的下调。”

Eguchi D.: "Mechanism of contraction induced by bradykinin in the rabbit saphenous vein." Br.J.Pharmacol.120. 371-378 (1997)

Eguchi D.：“缓激肽诱导兔隐静脉收缩的机制。”

Nishimura J: "The relaxant effect of adrenomedullin on particular smooth muscles despite a general expression of its mRNA in smooth muscle, endothelial and epithelial cells." Br.J.Pharmacol.120. 193-200 (1997)

Nishimura J：“肾上腺髓质素对特定平滑肌具有松弛作用，尽管其 mRNA 在平滑肌、内皮和上皮细胞中普遍表达。”