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钙离子通道的氧化还原调控:化学与生理方面。

Redox regulation of calcium ion channels: chemical and physiological aspects.

机构信息

Department of Biophysics, Saarland University, Homburg, Germany.

出版信息

Cell Calcium. 2011 Nov;50(5):407-23. doi: 10.1016/j.ceca.2011.07.006. Epub 2011 Sep 17.

DOI:10.1016/j.ceca.2011.07.006
PMID:21930299
Abstract

Reactive oxygen species (ROS) are increasingly recognized as second messengers in many cellular processes. While high concentrations of oxidants damage proteins, lipids and DNA, ultimately resulting in cell death, selective and reversible oxidation of key residues in proteins is a physiological mechanism that can transiently alter their activity and function. Defects in ROS producing enzymes cause disturbed immune response and disease. Changes in the intracellular free Ca(2+) concentration are key triggers for diverse cellular functions. Ca(2+) homeostasis thus needs to be precisely tuned by channels, pumps, transporters and cellular buffering systems. Alterations of these key regulatory proteins by reversible or irreversible oxidation alter the physiological outcome following cell stimulation. It is therefore necessary to understand which proteins are regulated and if this regulation is relevant in a physiological- and/or pathophysiological context. Because ROS are inherently difficult to identify and to measure, we first review basic oxygen redox chemistry and methods of ROS detection with special emphasis on electron paramagnetic resonance (EPR) spectroscopy. We then focus on the present knowledge of redox regulation of Ca(2+) permeable ion channels such as voltage-gated (CaV) Ca(2+) channels, transient receptor potential (TRP) channels and Orai channels.

摘要

活性氧(ROS)在许多细胞过程中被越来越多地认为是第二信使。虽然高浓度的氧化剂会损害蛋白质、脂质和 DNA,最终导致细胞死亡,但蛋白质中关键残基的选择性和可逆氧化是一种生理机制,可以暂时改变它们的活性和功能。ROS 产生酶的缺陷会导致免疫反应紊乱和疾病。细胞内游离 Ca(2+)浓度的变化是多种细胞功能的关键触发因素。因此,通道、泵、转运体和细胞缓冲系统需要精确地调节 Ca(2+)稳态。这些关键调节蛋白的可逆或不可逆氧化改变了细胞刺激后的生理结果。因此,有必要了解哪些蛋白质受到调节,以及这种调节在生理和/或病理生理背景下是否相关。由于 ROS 本质上难以识别和测量,我们首先回顾了基本的氧氧化还原化学和 ROS 检测方法,特别强调了电子顺磁共振(EPR)光谱。然后,我们将重点介绍目前关于电压门控(CaV)Ca(2+)通道、瞬时受体电位(TRP)通道和 Orai 通道等 Ca(2+)通透离子通道的氧化还原调节的知识。

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Redox regulation of calcium ion channels: chemical and physiological aspects.钙离子通道的氧化还原调控:化学与生理方面。
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