摘要
邻苯二酚胺对心功能的神经激素调节能加快心率并增强心脏收缩。然而,持续的肾上腺素紧张,会对心脏造成了一定的损伤,影响心脏的正常的动态平衡,改变其形态和以及基因表达模式,并可能诱发心肌细胞凋亡。与此同时,线粒体作为氧的主要消耗场所,线粒体也是生成维持心脏生命功能所需能量和整合一系列决定细胞存亡的信号通路的关键。就像α-肾上腺素受体(α-AR)可以对触发或抑制细胞死亡的多种生化反应产生协调作用一样,线粒体也可以在这整个过程中的充当调节者。实际上,α-AR的亚型α1和α2能激活各种下游通路,这些通路能有区别的调节细胞内钙水平和线粒体活性氧(ROS)的生成。心脏保护的自适应反应能增加心收缩力并激活生存通路,它与由钙引起的、ROS诱导线粒体破坏产生的细胞死亡之间存在微妙平衡,本文对该平衡及其临床依据和潜在的转化治疗方案进行了综述。
关键词: 细胞凋亡,α-肾上腺素能受体,钙,心肌细胞,线粒体,氧化应激
Current Drug Targets
Title:β-Adrenergic Over-Stimulation and Cardio-Myocyte Apoptosis: Two Receptors, One Organelle, Two Fates?
Volume: 15 Issue: 10
Author(s): Ana F. Branco, Ana C. Moreira, Teresa Cunha-Oliveira, Renata Couto, Vilma A. Sardao, Albert A. Rizvanov, Andras Palotas and Paulo J. Oliveira
Affiliation:
关键词: 细胞凋亡,α-肾上腺素能受体,钙,心肌细胞,线粒体,氧化应激
摘要: Neuro-hormonal regulation of cardiac function via cathecol-amines results in increased heart rate and contractility. A persistent adrenergic tone, however, is an insult to the heart, affecting its regular homeostasis, altering morphology and gene expression patterns, as well as inducing apoptosis of cardio-myocytes. At the same time as being the main oxygen consumers, mitochondria are also key to the energy production required for the heart to maintain its vital functions and to integrate a series of signaling pathways that define the life and death of the cell. As α-adrenergic receptors (α-AR) orchestrate multiple biochemical events that can either trigger or inhibit cell death, mitochondria can act as a referee in the entire process. In fact, α-AR subtypes α1 and α2 activate various down-stream pathways which differently modulate intracellular calcium levels and production of mitochondrial reactive oxygen species (ROS). The delicate balance between an adaptive (cardio-protective) response resulting in increased contractility and activation of survival pathways, vs. cell death caused by calcium and ROS-induced mitochondrial disruption, along with evidence of their clinical and potential therapeutic translations, are reviewed in this communication.
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Branco F. Ana, Moreira C. Ana, Cunha-Oliveira Teresa, Couto Renata, Sardao A. Vilma, Rizvanov A. Albert, Palotas Andras and Oliveira J. Paulo, β-Adrenergic Over-Stimulation and Cardio-Myocyte Apoptosis: Two Receptors, One Organelle, Two Fates?, Current Drug Targets 2014; 15 (10) . https://dx.doi.org/10.2174/1389450115666140902124230
DOI https://dx.doi.org/10.2174/1389450115666140902124230 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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