Role of caveolin located in the caveolae, identified as flask-shaped invaginations on the surface of the plasma membrane, involved in the mechanotrasduction of vascular system.

小凹蛋白的作用位于小凹，被确定为质膜表面的烧瓶状内陷，参与血管系统的机械传导。

• 批准号: 10672046
• 负责人: NAKAYAMA Koichi
• 金额: $ 2.11万
• 依托单位: Department of Pharmacology, Faculty op Pharmaceutical Sciences, University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672046/
• 关键词: hemodynamic stress; mechanotransduction; myogenic contraction; cerebral artery; caveola; caveolin; cellular signaling; cerebral vasospasm; カルシウム動態; インテグリン; チロシンキナーゼ; 脳動脈

Caveolae, identified as flask-shaped invaginations on the surface of the plasma membrane, have been considered to be hot spots for cell signaling, A variety of functional proteins, including ion channels, are localized in caveolae, and assembled with each other, resulting in expression of biological and pharmacological functions. We summarize herewith our results as following :1) Mechanotransduction and tyrosine kinase / tyrosine phosphorylation in cerebral and pulmonary arteries :The mechanisms of pressure-induced myogenic contraction was studied with regard to tyrosine phosphrylation were studied. Intracellular Ca concentration and vessel diameter were simultaneously measured. Furthermore, we tried to detect immunocytochemically in situ total tyrosine phosphorylation level and activity of pp60src in the arteries.2) Intracellular localization of protein kinase C isoforms in the contractile potentiation of coronary artery by agonistic stimuli and experimental cerebral vasospasm :Endoth … More elin 1 at a low concentration of 10-100pM potentiated 5-hydroxytryptamine-induced contraction of porcine coronary artery, which was consistent with translocation of protein kinase (PKC) a and d isoforms. Canine model of experimental cerebral vasospasm induced by injection of autologous blood injected into cisterna magna was also investigated with regard to PKC isoforms. PKC d was translocated to the membrane fraction during the development of the vasospasm, and PKC a was tanslocated in the late phase of established vasospasm. PKC a and d isoforms were densely located in caveolin-rich fraction. Furthermore, we suggest that mechanical stress such as stretch induces activation and down-regulation of PKC a in caveolae.3) Discussion and future development :The present results suggest that tyrosine kinase such as src family and PKC a and d isoforms assembles in caveolae and play a regulatory role in the expression of biological function such as contraction. We will improve the methods of immunocytochemical in situ detection and immunoprecipitation in the cardiovascular system. We will also develop a new pharmacological study aiming to detect simultaneously biological function and molecular dynamics in situ. Less

caveolae被认为是质膜表面上的烧瓶形，被认为是细胞信号的热点，含有离子通道的功能蛋白，并将其定位在小窝中，并与对方的生物学和药理学表达组装功能。我们总结了我们的结果：1）在脑和肺动脉中的机械传动和酪氨酸 / TY玫瑰磷酸化：对酪氨酸phrylation进行了压力诱导的肌源性收缩的机制。 2）蛋白激酶蛋白酶在动脉中的细胞内定位在Ronary动脉的收缩性刺激下通过激动刺激和实验性大脑血管痉挛：ELIN 1在低浓度的10-100pm耐高浓度的5--浓度的5-Hydroxypmine-Pmmine-Pmmine-contactine-poctine-ptactine-1冠状动脉与蛋白激酶（PKC）A和D同工型的易位一致。 PKC A在已建立的血管痉挛的晚期中被分配。结果表明，酪氨酸激酶（例如Caveolae中的SRC家族和PKC）在生物学功能的表达中发挥作用，例如收缩。原位功能和分子动力学

项目成果

N. Sakai, K. Nakayama, Y. Tanabe, S. Nishizawa, K. Uemura: "Absence of plasma protease-antiptotease imbalance in the formation of sacular cerebral aneurysms"Neurosurgry. 45. 34-39 (1999)

N. Sakai、K. Nakayama、Y. Tanabe、S. Nishizawa、K. Uemura：“在形成囊状脑动脉瘤时血浆蛋白酶-抗蛋白酶不平衡的缺失”神经外科。

K. Nakayama, Y. Fukuta, A. Kiyoshi, Y. Iwatsuki, K. Ishii, T. Ishikawa, M. Iida, H. Iwata, M. Enomoto: "(+)-[ィイD13ィエD1H]Isradipine and [ィイD13ィエD1H]glybenclamide bindings to heart and lung membranes from rats with monocrotaline-induced pulmonary hypertensi

K. Nakayama、Y. Fukuta、A. Kiyoshi、Y. Iwatsuki、K. Ishii、T. Ishikawa、M. Iida、H. Iwata、M. Enomoto：“(+)-[iiD13ieD1H]Isradipine 和 [D13D1H]glybenclamide与野百合碱诱导的肺动脉高压大鼠的心脏和肺膜结合

K. Obara, S. Hata, K. Sato, M. Koide, K. Ishii, K. Nakayama: "Contractile potentiation by endothelin-1 involves protein kinase C-d activity in porcine coronary artery."Japanese Journal of Physiology. 49. 175-183 (1999)

K. Obara、S. Hata、K. Sato、M. Koide、K. Ishii、K. Nakayama：“内皮素 1 的收缩增强涉及猪冠状动脉中的蛋白激酶 C-d 活性。”《日本生理学杂志》。

M.Saito,Y.Tanabe,N.Masumoto,T.Ishikawa,K.Obara,N.Horie,K.Takeishi,K.Nakayama: "Differential augmentation of tyrosine phosphorylation by mechanical stretch in smooth muscle and endothelial cells of rabbit pulmonary arteries. (abstract)" Japanese Journal of

M.Saito，Y.Tanabe，N.Masumoto，T.Ishikawa，K.Obara，N.Horie，K.Takeishi，K.Nakayama：“机械拉伸对兔肺平滑肌和内皮细胞酪氨酸磷酸化的差异增强

N.Sakai,K.Nakayama,Y.Tanabe,S.Nishizawa,K.Uemura: "Absence of plasma protease-antiprotease imbalance in the formation of saccular cerebral aneurysms"Neurosurgry. 45. 34-39 (1999)

N.Sakai、K.Nakayama、Y.Tanabe、S.Nishizawa、K.Uemura：“囊状脑动脉瘤形成过程中血浆蛋白酶-抗蛋白酶不平衡的缺失”神经外科。