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RESEARCH FOR ALTERATION OF G-PROTEIN GENE IN MYOCARDOPATHY

心肌病中 G 蛋白基因的改变研究

基本信息

批准号：
06454283
负责人：
KAWAGUCHI Hideaki
金额：
$ 4.74万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454283/
关键词：
G PROTEIN CARDIOMYOPATHY CARDIAC FAILURE beta ADRENERGIC RECEPTOR DILATED CARDIOMYOPATHY GENE beta ADRENERGIC RECEPTOR KINASE (betaARK)

项目摘要

G protein serve as transducers between cell surface receptors and intracellular effectors. They consist of three subunits. The desensitization and down-regulation of beta-adrenergic receptor kinase (betaARK). The desensitization and down-regulation of beta-adrenergic receptors (betaAR) have been observed in the heart failure. betaARK is one of the components involved in desensitization of betaAR.G protein betagamma subunit bind betaARK through the pleckstrin homonogy domein. Therefore, we investigated the effects of beta AR stimulation on steady-state level G protein beta subunit (Gbeta) in the rat heart. The whole rat heart was perfused by Langendorff's techniqe with the indicated agents. Immunoblotting using isoform-specific antisera against G protein beta subunits revealed that the rat heart containings at least three G protein beta subunits, beta1, beta2, beta3. The level of Gbeta3 in the cytosol dramatically decreased in the presence of ISO alone or ISO with cGP.Gbeta3 decreased in the presence of EPI as well. Propranolol could blockISO-induced decrease of Gbeta3 in the cytosol. In contrast, the levels of Gbeta1 and Gbeta2 did not change in the presence of ISO or EPI.On the other hand, in membrane fractions the level of Gbeta3 significantly increased in the presence of ISO or EPI.ISO with propranolol or ISO with CGP did not change the level of Gbeta3 in membrane fraction. The levels of Gbeta1 and Gbeta2 did not change in the presence of ISO or EPI in membrane fractions. Taken together, betaAR agonist might induce isoform-specific translocation of Gbeta3 from the cyctosol to the membrane.

G蛋白作为细胞表面受体和细胞内效应物之间的转换器。它们由三个分股组成。β-肾上腺素能受体激酶（betaARK）的脱敏和下调。在心力衰竭中观察到β-肾上腺素能受体（beta-adrenergic receptor，β AR）的脱敏和下调。β ARK是参与β AR脱敏的组分之一，G蛋白β γ亚基通过pleckstrin同源蛋白结合β ARK。因此，我们研究了β AR刺激对大鼠心脏中稳态水平G蛋白β亚基（G β）的影响。采用Langendorff法对大鼠心脏进行灌流。使用同种型特异性抗血清对G蛋白β亚基的免疫印迹显示，大鼠心脏含有至少三个G蛋白β亚基，β 1，β 2，β 3。在单独的ISO或ISO与cGP的存在下，胞浆中的G β 3水平显著降低，在EPI的存在下，G β 3也降低。普萘洛尔可阻断ISO诱导的胞浆中G β 3的减少。与此相反，G β 1和G β 2在ISO或EPI的存在下没有变化，另一方面，在膜组分中G β 3的水平在ISO或EPI的存在下显著增加，ISO与普萘洛尔或ISO与CGP没有改变膜组分中G β 3的水平。在膜组分中存在ISO或EPI时，Gbeta 1和Gbeta 2的水平没有变化。综上所述，β AR激动剂可能诱导Gbeta 3从胞质溶胶到膜的异构体特异性易位。