Cardiac mitochondrial dysfunction during hyperglycemia-The role of oxidative stress and p66Shc signaling
Cardiac mitochondrial dysfunction during hyperglycemia-The role of oxidative stress and p66Shc signaling
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DOI：
10.1016/j.biocel.2012.07.004
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Wieckowski, Mariusz R.
中科院分区：
文献类型：
--
作者：
Diogo, Catia V.;Suski, Jan M.;Wieckowski, Mariusz R.
糖尿病是一种由胰岛素产生不足和/或胰岛素抵抗作用引起的慢性疾病。胰岛素缺乏导致的高血糖症是糖尿病心血管并发症的主要引发因素，随着时间的推移，糖尿病心血管并发症由许多复杂的生化和分子过程驱动。四种假说，提出了糖尿病相关的病理生理机制，目前正在考虑。心血管损害可能由多元醇途径通量增加、细胞内晚期糖基化终产物形成或通过己糖胺途径的通量增加引起。这些机制中的后者涉及蛋白激酶C的活化。在糖尿病过程中观察到的细胞和线粒体代谢改变部分与活性氧（ROS）的过度产生相关。在参与ROS产生的许多过程和因素中，生长因子衔接子shc（p66 Shc蛋白）的66 kDa同种型特别令人感兴趣。这种蛋白质在控制糖尿病依赖性氧化平衡中起关键作用，因此最近对其参与糖尿病并发症和其他基于氧化应激的病理学进行了深入研究。在这篇综述中，我们总结了目前的认识，高血糖引起的心脏线粒体功能障碍的氧化应激和p66 Shc蛋白的重点。这篇文章的一部分，定向问题，题为：生物能量障碍，适应和治疗。(C)2012爱思唯尔有限公司保留所有权利。
Diabetes mellitus is a chronic disease caused by a deficiency in the production of insulin and/or by the effects of insulin resistance. Insulin deficiency leads to hyperglycemia which is the major initiator of diabetic cardiovascular complications escalating with time and driven by many complex biochemical and molecular processes. Four hypotheses, which propose mechanisms of diabetes-associated pathophysiology, are currently considered. Cardiovascular impairment may be caused by an increase in polyol pathway flux, by intracellular advanced glycation end-products formation or increased flux through the hexosamine pathway. The latter of these mechanisms involves activation of the protein kinase C.Cellular and mitochondrial metabolism alterations observed in the course of diabetes are partially associated with an excessive production of reactive oxygen species (ROS). Among many processes and factors involved in ROS production, the 66 kDa isoform of the growth factor adaptor shc (p66Shc protein) is of particular interest. This protein plays a key role in the control of mitochondria-dependent oxidative balance thus it involvement in diabetic complications and other oxidative stress based pathologies is recently intensively studied. In this review we summarize the current understanding of hyperglycemia induced cardiac mitochondrial dysfunction with an emphasis on the oxidative stress and p66Shc protein.This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. (C) 2012 Elsevier Ltd. All rights reserved.