摘要
最近,由于使食欲减退和抗高血糖的特点,下丘脑82-aa肽Nesfatin-1受到显著的关注。Nesfatin-1在哺乳动物的下丘脑表达,连同前体Nucleobindin 2(NUCB2)局部控制食品的摄入量、体重和葡萄糖体内平衡。在老鼠心脏,该肽也是局部地表达并和NUCB2共同存在。除了主要的营养和能量平衡调节,以及神经电路中负责控制血压和心率的调节,Nesfatin-1也影响周边的几个区域,包括心血管系统(CV)。因此,该肽被认为是多功能激素,其不仅仅参与与体内滋养平衡。本文旨在分析Nesfatin-1文献,关注其新兴的心血管系统研究。 一些研究表明,该肽能够影响小鼠和人类心肌细胞的能量代谢,引起胰岛素样作用。在离体大鼠心脏,它通过cGMP、PKG和ERK1/2直接降低了收缩和舒张性,并限制缺血/再灌注(I/ R)损伤,作用于后处理保护。针对Nesfatin-1的行为提出其与一个未知的G蛋白耦合的受体相关。然而,在大鼠的心、功能研究,免疫共沉淀和局部序列比对分析表明其与NPR-A相互作用有关。这些数据生成了新的角度,不仅阐明肽的生物学意义,而且公认其在营养依赖型心血管疾病的生物医学潜力。
关键词: 神经肽,心血管生理学,心肌保护
Current Drug Targets
Title:Nesfatin-1 and the Cardiovascular System: Central and Pheripheral Actions and Cardioprotection
Volume: 16 Issue: 8
Author(s): Sandra Imbrogno, Tommaso Angelone and Maria C. Cerra
Affiliation:
关键词: 神经肽,心血管生理学,心肌保护
摘要: Recently, the hypothalamic 82-aa peptide Nesfatin-1 received notable attention for its anorexigenic and anti-hyperglycemic properties. In mammalian hypothalamus, Nesfatin-1 is expressed, together with the precursor Nucleobindin 2 (NUCB2), in regions controlling water-food intake, body weight, and glucose homeostasis. The peptide is also peripherally expressed, as shown in the rat heart, in which it is present together with NUCB2. In addition to a central modulation of nutrition and energy balance, and of the nervous circuits responsible for blood pressure and heart rate control, Nesfatin-1 also acts peripherally on several districts, including the cardiovascular (CV) system. Accordingly, the peptide is regarded with interest as a multifunctional hormone not only linked to alimentary homeostasis. This review aims to analyze the literature on Nesfatin-1, with focus on its emerging CV activity. Few available studies show that the peptide affects energy metabolism of murine and human cardiomyocytes, by eliciting insulin-like effects. On the ex vivo rat heart, it directly depresses contractility and relaxation via cGMP, PKG and ERK1/2, and limits ischemia/reperfusion (I/R) damage, acting in post-conditioning protection. Nesfatin-1 actions are proposed to involve an unknown G-protein coupled receptor. However, in the rat heart, functional studies, co-immunoprecipitation and local sequence alignment analyses suggest an interaction with the Natriuretic Peptide Receptor-type A (NPR-A). These data open up novel perspectives to clarify not only the biological significance of the peptide, but also its putative biomedical potential in the presence of nutrition-dependent cardiovascular diseases.
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Sandra Imbrogno, Tommaso Angelone and Maria C. Cerra , Nesfatin-1 and the Cardiovascular System: Central and Pheripheral Actions and Cardioprotection, Current Drug Targets 2015; 16 (8) . https://dx.doi.org/10.2174/1389450116666150408101431
DOI https://dx.doi.org/10.2174/1389450116666150408101431 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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