Proteostasis and REDOX state in the heart
Proteostasis and REDOX state in the heart
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DOI：
10.1152/ajpheart.00903.2011
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发表时间：
2012-01-01
影响因子：
4.8
通讯作者：
Benjamin, Ivor J.
中科院分区：
文献类型：
--
作者：
Christians, Elisabeth S.;Benjamin, Ivor J.
christian ES, Benjamin IJ。心脏的蛋白质停滞和氧化还原状态。[J]中国生物医学工程学报，2012,31(2):444 - 444。首次发表于2011年10月14日；doi: 10.1152 / ajpheart.00903.2011。在机体的整个生命周期中，产生力的心肌收缩细胞必须实现并维持其作为高效机械泵的主要功能。因为在整个人的一生中，只有一半的心肌细胞可以被替换，因此心肌细胞的维持策略依赖于其成分的不间断更新，包括蛋白质，这些蛋白质的特殊功能构成了这种复杂而复杂的收缩装置。因此，心脏蛋白不断合成和降解，以确保蛋白质组的稳态，也称为“蛋白质稳态”。一旦合成，蛋白质经过额外的折叠、翻译后修饰、运输和/或参与蛋白质-蛋白质或蛋白质- dna相互作用以发挥其功能。这包括心脏蛋白与分子伴侣的关键瞬态相互作用，这有助于在多个水平上进行质量控制，以防止错误折叠或促进降解。重要的是，心脏蛋白质组的维持取决于细胞环境，特别是还原氧化（REDOX）状态，这在心脏细胞器（如线粒体和内质网）中有显著差异。考虑到线粒体对氧气消耗和ATP产生的高代谢活性，心脏细胞在保持氧化还原状态的同时防止过度的氧化或还原性应激是一个挑战。受到干扰的氧化还原环境会影响蛋白质的处理和构象（如二硫键），破坏关键的结构-功能关系，并引发蛋白质聚集的致病级联反应，降低细胞存活率，增加器官功能障碍。这篇综述涵盖了目前关于氧化还原状态和蛋白质折叠的一般领域的知识，特别是在正常健康状态下和与人类发病率和死亡率相关的疾病状态下的心肌细胞。
Christians ES, Benjamin IJ. Proteostasis and REDOX state in the heart. Am J Physiol Heart Circ Physiol 302: H24-H37, 2012. First published October 14, 2011; doi:10.1152/ajpheart.00903.2011.-Force-generating contractile cells of the myocardium must achieve and maintain their primary function as an efficient mechanical pump over the life span of the organism. Because only half of the cardiomyocytes can be replaced during the entire human life span, the maintenance strategy elicited by cardiac cells relies on uninterrupted renewal of their components, including proteins whose specialized functions constitute this complex and sophisticated contractile apparatus. Thus cardiac proteins are continuously synthesized and degraded to ensure proteome homeostasis, also termed "proteostasis." Once synthesized, proteins undergo additional folding, posttranslational modifications, and trafficking and/or become involved in protein-protein or protein-DNA interactions to exert their functions. This includes key transient interactions of cardiac proteins with molecular chaperones, which assist with quality control at multiple levels to prevent misfolding or to facilitate degradation. Importantly, cardiac proteome maintenance depends on the cellular environment and, in particular, the reduction-oxidation (REDOX) state, which is significantly different among cardiac organelles (e. g., mitochondria and endoplasmic reticulum). Taking into account the high metabolic activity for oxygen consumption and ATP production by mitochondria, it is a challenge for cardiac cells to maintain the REDOX state while preventing either excessive oxidative or reductive stress. A perturbed REDOX environment can affect protein handling and conformation (e. g., disulfide bonds), disrupt key structure-function relationships, and trigger a pathogenic cascade of protein aggregation, decreased cell survival, and increased organ dysfunction. This review covers current knowledge regarding the general domain of REDOX state and protein folding, specifically in cardiomyocytes under normal-healthy conditions and during disease states associated with morbidity and mortality in humans.