摘要
在代谢性疾病如肥胖症,代谢综合征和II型糖尿病中,解偶联蛋白(UCPs)在线粒体呼吸复合物增加活性氧(ROS)产生的反应中的过表达以及过量游离脂肪酸( FFA)从脂肪组织供应,可以保护细胞免受氧化应激,脂毒性和死亡。 UCPs通过减少超氧阴离子和H2O2的产生触发了几种信号传递给细胞以适应脂毒性微环境。在线粒体中,细胞色素c(细胞色素c)和促凋亡蛋白释放的减少促进细胞存活和增殖。改变的脂质代谢还影响心磷脂对过氧化作用的易感性,该过程涉及细胞色素从线粒体内膜的解离及其释放,细胞凋亡的关键步骤。因此,通过减少ROS产生和脂毒性的UCPs可以下调程序性细胞死亡,这是众所周知的控制细胞增殖的生理过程,有助于不受控制的细胞增殖和肿瘤发生。此外,通过抑制ROS产生的肿瘤细胞过度表达UCP,在用氧化应激药物诱导剂进行药理治疗期间获得对死亡的抗性。因此,本综述的目的是通过保护免受ROS产生和保持生物能代谢稳态以促进细胞增殖来讨论关于UCP在细胞存活中的作用的最新发现。
关键词: 细胞凋亡,细胞色素c释放,氧化应激,解偶联蛋白,肥胖症,癌症.
Current Molecular Medicine
Title:Uncoupling Protein Overexpression in Metabolic Disease and the Risk of Uncontrolled Cell Proliferation and Tumorigenesis
Volume: 17 Issue: 9
关键词: 细胞凋亡,细胞色素c释放,氧化应激,解偶联蛋白,肥胖症,癌症.
摘要: In metabolic diseases such as obesity, metabolic syndrome and type II diabetes, the over-expression of uncoupling proteins (UCPs) in a response to increased reactive oxygen species (ROS) generation by mitochondrial respiratory complexes, and to the excess of free fatty acid (FFA) supply from adipose tissue, may protect cells from oxidative stress, lipotoxicity and in turn from death. UCPs by reducing superoxide anion and H2O2 generation trigger several signals to cell for their adaptation to the lipotoxic microenvironment. In mitochondria, a decrease of cytochrome c (cyt c) and proapoptotic protein release promotes cell survival and proliferation. The altered lipid metabolism also affects cardiolipin susceptibility to the peroxidation, a process involved in the dissociation of cyt c from mitochondrial inner membrane and its release, a key step of apoptosis. Therefore, UCPs by attenuating ROS generation and lipotoxicity may downregulate programmed cell death, a well-known physiological process controlling cell proliferation contributing to uncontrolled cell proliferation and tumorigenesis. In addition, tumor cells over-expressed UCPs, by inhibiting ROS generation acquire resistance to death during pharmacological treatment with oxidative stress drug inducers. Therefore, the aim of this review is to discuss recent findings regarding the role that UCPs play in cell survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote cell proliferation.
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Cite this article as:
Uncoupling Protein Overexpression in Metabolic Disease and the Risk of Uncontrolled Cell Proliferation and Tumorigenesis, Current Molecular Medicine 2017; 17 (9) . https://dx.doi.org/10.2174/1566524018666180308110822
DOI https://dx.doi.org/10.2174/1566524018666180308110822 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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