Small heat shock proteins in redox metabolism: implications for cardiovascular diseases.
Small heat shock proteins in redox metabolism: implications for cardiovascular diseases.
复制标题
DOI：
10.1016/j.biocel.2012.06.006
复制
发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Benjamin IJ
中科院分区：
文献类型：
--
作者：
Christians ES;Ishiwata T;Benjamin IJ
由于该伴侣家族的几个成员在心肌和血管中表现出强烈的表达，因此对小热休克蛋白的及时回顾系列必须适当地检查它们的基本特性和对心血管系统的影响。由于能量和代谢需求，心血管系统保持较高的线粒体活性，但活性氧产生的增加可能会导致不可逆的氧化损伤。如何实现它们的产生和清除之间的平衡对于生理维持至关重要。例如，热休克蛋白 B1 (HSPB1) 通过维持主要氧化还原介质谷胱甘肽的水平来维持这种平衡或氧化还原稳态。通过基因操作获得或丧失功能的研究对于理解这些蛋白质的作用提供了丰富的信息。例如，几种小型热休克蛋白（例如 HSPB5 和 HSPB2）的遗传缺陷在心脏细胞中具有良好的耐受性，而单个错义突变则会导致人类病理学。这些证据强调了在小热休克蛋白的多基因家族中观察到的深刻的遗传冗余，同时强调了蛋白质毒性在驱动疾病发病机制中的作用。我们将讨论心血管系统、氧化还原代谢和人类疾病中小热休克蛋白的现有数据。从医学角度来看，我们预计，这种关于小热休克蛋白在心血管系统中发挥的多种作用的新知识无疑将为它们的识别和人类可能的治疗靶向开辟新的途径。
A timely review series on small heat shock proteins has to appropriately examine their fundamental properties and implications in the cardiovascular system since several members of this chaperone family exhibit robust expression in the myocardium and blood vessels. Due to energetic and metabolic demands, the cardiovascular system maintains a high mitochondrial activity but irreversible oxidative damage might ensue from increased production of reactive oxygen species. How equilibrium between their production and scavenging is achieved becomes paramount for physiological maintenance. For example, heat shock protein B1 (HSPB1) is implicated in maintaining this equilibrium or redox homeostasis by upholding the level of glutathione, a major redox mediator. Studies of gain or loss of function achieved by genetic manipulations have been highly informative for understanding the roles of those proteins. For example, genetic deficiency of several small heat shock proteins such as HSPB5 and HSPB2 is well-tolerated in heart cells whereas a single missense mutation causes human pathology. Such evidence highlights both the profound genetic redundancy observed among the multigene family of small heat shock proteins while underscoring the role proteotoxicity plays in driving disease pathogenesis. We will discuss the available data on small heat shock proteins in the cardiovascular system, redox metabolism and human diseases. From the medical perspective, we envision that such emerging knowledge of the multiple roles small heat shock proteins exert in the cardiovascular system will undoubtedly open new avenues for their identification and possible therapeutic targeting in humans.
登录
查看更多内容
影响因子：
11.2
作者：
Del Bigio, Marc R.;Chudley, Albert E.;Selcen, Duygu
通讯作者：
Selcen, Duygu
DOI：
10.1152/ajpheart.00514.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Banerjee, Indroneal;Fuseler, John W.;Baudino, Troy A.
通讯作者：
Baudino, Troy A.
影响因子：
9.8
作者：
Berry, V;Francis, P;Quinlan, RA
通讯作者：
Quinlan, RA
影响因子：
5
作者：
Armstrong, SC;Shivell, LC;Ganote, CE
通讯作者：
Ganote, CE
DOI：
10.1152/ajpheart.00903.2011
发表时间：
2012-01-01
影响因子：
4.8
作者：
Christians, Elisabeth S.;Benjamin, Ivor J.
通讯作者：
Benjamin, Ivor J.