期刊
CELLULAR AND MOLECULAR NEUROBIOLOGY
卷 38, 期 1, 页码 109-120出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-017-0557-2
关键词
Environmental stress; Aging; Heart failure; Adrenergic receptors; Sirtuins
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo Research Foundation) [2012/21990-6, 2016/20777-8]
- Fundacao de Amparo a Pesquisa do Espirito Santo (FAPES, Foundation for the Support of Research in the State of Espirito Santo) [74087886]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, National Council for Scientific and Technological Development) [424114/2016-0]
In the heart, catecholamine effects occur by activation of beta-adrenergic receptors (beta-ARs), mainly the beta 1 (beta(1)-AR) and beta 2 (beta(2)-AR) subtypes, both of which couple to the Gs protein that activates the adenylyl cyclase signaling pathway. The beta(2)-ARs can also couple to the Gi protein that counterbalances the effect of the Gs protein on cyclic adenosine monophosphate production and activates the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. In several cardiovascular disorders, including heart failure, as well as in aging and in animal models of environmental stress, a reduction in the beta(1)/beta(2)-AR ratio and activation of the beta(2)-AR-Gi-PI3K-Akt signaling pathway have been observed. Recent studies have shown that sirtuins modulate certain organic processes, including the cellular stress response, through activation of the PI3K-Akt signaling pathway and of downstream molecules such as p53, Akt, HIF1-alpha, and nuclear factor-kappa B. In the heart, SIRT1, SIRT3, and beta(2)-ARs are crucial to the regulation of the cardiomyocyte energy metabolism, oxidative stress, reactive oxygen species production, and autophagy. SIRT1 and the beta(2)-AR-Gi complex also control signaling pathways of cell survival and death. Here, we review the role played by beta(2)-ARs and sirtuins during aging, heart failure, and adaptation to stress, focusing on the putative interplay between the two. That relationship, if proven, merits further investigation in the context of cardiac function and dysfunction.
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