Hydrogen Peroxide Sensing and Signaling by Protein Kinases in the Cardiovascular System

被引:166
作者
Burgoyne, Joseph R. [1 ]
Oka, Shin-ichi [2 ]
Ale-Agha, Niloofar [3 ]
Eaton, Philip [1 ]
机构
[1] Kings Coll London, Dept Cardiol, Rayne Inst, St Thomas Hosp, London SE1 7EH, England
[2] Univ Med & Dent New Jersey, New Jersey Med Sch, Cardiovasc Res Inst, Dept Cell Biol & Mol Med, Newark, NJ 07103 USA
[3] Univ Dusseldorf gGmbH, IUF, Dept Mol Cell & Aging Res, Dusseldorf, Germany
基金
英国医学研究理事会;
关键词
CYSTEINE-SULFINIC ACID; OXIDATIVE STRESS; EXPIRED BREATH; REDOX REGULATION; ALPHA; H2O2; REVEALS; ACTIVATION; SUBUNIT; PEROXIREDOXINS;
D O I
10.1089/ars.2012.4817
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Significance: Oxidants were once principally considered perpetrators of injury and disease. However, this has become an antiquated view, with cumulative evidence showing that the oxidant hydrogen peroxide serves as a signaling molecule. Hydrogen peroxide carries vital information about the redox state of the cell and is crucial for homeostatic regulation during health and adaptation to stress. Recent Advances: In this review, we examine the contemporary concepts for how hydrogen peroxide is sensed and transduced into a biological response by introducing post-translational oxidative modifications on select proteins. Oxidant sensing and signaling by kinases are of particular importance as they integrate oxidant signals into phospho-regulated pathways. We focus on CAMKII, PKA, and PKG, kinases whose redox regulation has notable impact on cardiovascular function. Critical Issues: In addition, we examine the mechanism for regulating intracellular hydrogen peroxide, considering the net concentrations that may accumulate. The effects of endogenously generated oxidants are often modeled by applying exogenous hydrogen peroxide to cells or tissues. Here we consider whether model systems exposed to exogenous hydrogen peroxide have relevance to systems where the oxidant is generated endogenously, and if so, what concentration can be justified in terms of relevance to health and disease. Future Directions: Improving our understanding of hydrogen peroxide signaling and the sensor proteins that it can modify will help us develop new strategies to regulate intracellular signaling to prevent disease. Antioxid. Redox Signal. 18, 1042-1052.
引用
收藏
页码:1042 / 1052
页数:11
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