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调节蛋白G蛋白偶联受体激酶2和β-抑制蛋白1在大鼠出生后脑发育过程中的表达模式:甲状腺功能减退的影响

Expression patterns of the regulatory proteins G protein-coupled receptor kinase 2 and beta-arrestin 1 during rat postnatal brain development: effect of hypothyroidism.

作者信息

Penela P, Alvarez-Dolado M, Muñoz A, Mayor F

机构信息

Departamento de Biología Molecular, Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Universidad Autónoma de Madrid, Spain.

出版信息

Eur J Biochem. 2000 Jul;267(14):4390-6. doi: 10.1046/j.1432-1327.2000.01484.x.

Abstract

G protein-coupled receptor kinase 2 (GRK2) and beta-arrestin 1 are key regulatory proteins that modulate the desensitization and resensitization of a wide variety of G protein-coupled receptors (GPCRs) involved in brain functions. In this report, we describe the postnatal developmental profile of the mRNA and protein levels of GRK2 and beta-arrestin 1 in rat brain. The expression levels of GRK2 and beta-arrestin 1 display a marked increase at the second and third week after birth, respectively, consistent with an involvement of these proteins in brain maturation processes. However, the expression attained at birth and during the first postnatal week with respect to adult values (45-70% for GRK2, approximately 30% for beta-arrestin 1) is relatively high compared to that reported for several GPCRs, indicating the existence of changes in the ratio of receptors to their regulatory proteins during brain development. On the other hand, we report that experimental hypothyroidism results in changes in the patterns of expression of GRK2 and beta-arrestin 1 in cerebral cortex, leading to a 25-30% reduction in GRK2 levels at several stages of development. Such changes could help to explain the alterations in GPCR signaling that occur during this pathophysiological condition.

摘要

G蛋白偶联受体激酶2(GRK2)和β-抑制蛋白1是关键的调节蛋白,可调节参与脑功能的多种G蛋白偶联受体(GPCR)的脱敏和再敏化。在本报告中,我们描述了大鼠脑中GRK2和β-抑制蛋白1的mRNA和蛋白质水平的出生后发育情况。GRK2和β-抑制蛋白1的表达水平分别在出生后的第二周和第三周显著增加,这与这些蛋白质参与脑成熟过程一致。然而,与几种GPCR报道的情况相比,出生时和出生后第一周相对于成年值的表达(GRK2为45-70%,β-抑制蛋白1约为30%)相对较高,表明在脑发育过程中受体与其调节蛋白的比例存在变化。另一方面,我们报告实验性甲状腺功能减退会导致大脑皮质中GRK2和β-抑制蛋白1的表达模式发生变化,导致在几个发育阶段GRK2水平降低25-30%。这些变化有助于解释在这种病理生理状况下发生的GPCR信号转导改变。

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