β-Adrenergic Over-Stimulation and Cardio-Myocyte Apoptosis: Two Receptors, One Organelle, Two Fates?
β-Adrenergic Over-Stimulation and Cardio-Myocyte Apoptosis: Two Receptors, One Organelle, Two Fates?
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DOI：
10.2174/1389450115666140902124230
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发表时间：
2014-01-01
影响因子：
3.2
通讯作者：
Oliveira, Paulo J.
中科院分区：
文献类型：
--
作者：
Branco, Ana F.;Moreira, Ana C.;Oliveira, Paulo J.
通过儿茶酚胺对心脏功能的神经激素调节导致心率和收缩力增加。然而，持续的肾上腺素能紧张是对心脏的一种损害，影响其正常的稳态，改变形态和基因表达模式，以及诱导心肌细胞凋亡。同时作为主要的氧消耗者，线粒体也是心脏维持其重要功能所需的能量产生的关键，并整合了一系列定义细胞生死的信号通路。由于β-肾上腺素能受体（β-AR）协调多种生物化学事件，可以触发或抑制细胞死亡，线粒体可以在整个过程中充当裁判。事实上，β-AR亚型β（1）和β（2）激活各种下游途径，这些途径不同地调节细胞内钙水平和线粒体活性氧（ROS）的产生。适应性（心脏保护）反应之间的微妙平衡，导致增加的收缩性和激活的生存途径，与细胞死亡引起的钙和ROS诱导的线粒体破坏，沿着其临床和潜在的治疗翻译的证据，审查在此通信。
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 beta-adrenergic receptors (beta-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, beta-AR subtypes beta(1) and beta(2) 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.