由β-阿司匹林介导的β-肾上腺素能受体信号转导及其在心力衰竭中的潜在作用

IF 2.5 Q2 PHYSIOLOGY
Preston C Nibley , Sudha K Shenoy
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引用次数: 0

摘要

心力衰竭的致死率很高,尤其是在急性后遗症 SARS-CoV-2 感染相关心肌炎的情况下,因此有必要发现与心血管疾病有关的细胞通路。我们总结了儿茶酚胺结合型β-肾上腺素能受体(β-ARs)的信号传导机制,重点是β-阻遏素的作用。β-ARs是G蛋白偶联受体(GPCRs)的一个子集,通常通过异三聚体G蛋白传播信号。然而,自 20 世纪 80 年代末发现以来,β-arrestins 已被证明既能(i)淬灭 G 蛋白信号,又能(ii)启动其自身独立的信号级联,这受到翻译后修饰的影响。β-受体阻滞剂卡维地洛(carvedilol)的β-restin-biased激动作用及其异位调节作用可起到保护心脏的作用。GPCR 信号转导的迷宫性质日益明显,这表明配体依赖的 β-AR 信号转导要么受到激动剂的刺激,要么受到拮抗剂的阻断,并通过异构调节选择性地增强或抑制,而异构调节是由新型药物或内源性翻译后修饰精心策划的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
β-adrenergic receptor signaling mediated by β-arrestins and its potential role in heart failure

The lethality of heart failure, particularly in the context of post-acute sequelae SARS-CoV-2 infection-related myocarditis, necessitates the discovery of the cellular pathways implicated in cardiovascular disease. We summarize the signaling mechanisms of the catecholamine-binding β-adrenergic receptors (β-ARs), with an emphasis on the role of β-arrestins. β-ARs, a subset of G protein-coupled receptors (GPCRs), canonically propagate signals through heterotrimeric G proteins. However, since their discovery in the late 1980s, β-arrestins have been shown to both (i) quench G protein signaling and (ii) initiate their own independent signaling cascades, which is influenced by posttranslational modifications. β-arrestin-biased agonism by the beta-blocker carvedilol and its allosteric modulation can serve a cardioprotective role. The increasingly labyrinthine nature of GPCR signaling suggests that ligand-dependent β-AR signaling, either stimulated by an agonist or blocked by an antagonist, is selectively enhanced or suppressed by allosteric modulations, which are orchestrated by novel drugs or endogenous posttranslational modifications.

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来源期刊
Current Opinion in Physiology
Current Opinion in Physiology Medicine-Physiology (medical)
CiteScore
5.80
自引率
0.00%
发文量
52
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