The role of angiotensin AT1 receptor-associated protein in renin-angiotensin system regulation and function
The role of angiotensin AT1 receptor-associated protein in renin-angiotensin system regulation and function
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DOI：
10.1007/s11906-007-0022-6
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发表时间：
2007-04-01
影响因子：
5.6
通讯作者：
Matsuda, Miyuki
中科院分区：
文献类型：
--
作者：
Tamura, Kouichi;Tanaka, Yutaka;Matsuda, Miyuki
我们克隆了一种新的分子，AT 1受体相关蛋白（ATRAP），它在许多组织中表达，但特异性地与AT 1受体羧基端相互作用。在肾脏中，ATRAP广泛分布于沿着肾小管，盐摄入调节其表达。在心血管细胞中，血管紧张素II（Ang II）刺激使ATRAP与AT 1受体共定位于细胞质中，ATRAP过表达降低细胞表面AT 1受体。在下游信号通路中，ATRAP抑制血管紧张素II诱导的丝裂原活化蛋白激酶的磷酸化，c-fos基因转录的激活，以及心血管细胞中氨基酸或溴脱氧尿苷掺入的增强。因此，心血管ATRAP可以促进AT 1受体内化，减弱Ang II介导的心血管重塑。ATRAP有望成为治疗和预防高血压心血管重构的新靶分子。
We cloned a novel molecule, AT1 receptor-associated protein (ATRAP), which is expressed in many tissues but specifically interacts with the AT1 receptor carboxyl-terminal. In the kidney, ATRAP was broadly distributed along the renal tubules, salt intake modulated its expression. In cardiovascular cells, angiotensin II (Ang II) stimulation made ATRAP co-localized with AT1 receptor in cytoplasm; ATRAP overexpression decreased cell surface AT1 receptor. In downstream signaling pathways, ATRAP suppressed Ang II-induced phosphorylation of mitogen-activated protein kinase, activation of c-fos gene transcription, and enhancement of amino acid or bromodeoxyuridine incorporation in cardiovascular cells. Thus, cardiovascular ATRAP may promote AT1 receptor internalization and attenuate Ang II-mediated cardiovascular remodeling. We would expect ATRAP to become a new therapeutic target molecule to treat and prevent cardiovascular remodeling in hypertension.