哺乳动物细胞中信号蛋白的直接氧化修饰及其对细胞凋亡的影响。

Direct oxidative modifications of signalling proteins in mammalian cells and their effects on apoptosis.

作者信息

England K, Cotter T G

机构信息

Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland.

出版信息

Redox Rep. 2005;10(5):237-45. doi: 10.1179/135100005X70224.

Abstract

The production of ROS is an inevitable consequence of metabolism. However, high levels of ROS within a cell can be lethal and so the cell has a number of defences against oxidative cell stress. Occasionally the cell's antioxidant mechanisms fail and oxidative stress occurs. High levels of ROS within a cell have a number of direct and indirect consequences on cell signalling pathways and may result in apoptosis or necrosis. Although some of the indirect effects of ROS are well known, limitations in technology mean that the direct effects of the cell's redox environment upon proteins are less understood. Recent work by a number of groups has demonstrated that ROS can directly modify signalling proteins through different modifications, for example by nitrosylation, carbonylation, di-sulphide bond formation and glutathionylation. These modifications modulate a protein's activity and several recent papers have demonstrated their importance in cell signalling events, especially those involved in cell death/survival. Redox modification of proteins allows for further regulation of cell signalling pathways in response to the cellular environment. Understanding them may be critical for us to modulate cell pathways for our own means, such as in cytotoxic drug treatments of cancer cells. Protein modifications mediated by oxidative stress can modulate apoptosis, either through specific protein modifications resulting in regulation of signalling pathways, or through a general increase in oxidised proteins resulting in reduced cellular function. This review discusses direct oxidative protein modifications and their effects on apoptosis.

摘要

活性氧(ROS)的产生是新陈代谢不可避免的结果。然而,细胞内高水平的ROS可能是致命的,因此细胞有多种防御氧化应激的机制。偶尔,细胞的抗氧化机制会失效,从而发生氧化应激。细胞内高水平的ROS会对细胞信号通路产生许多直接和间接的影响,并可能导致细胞凋亡或坏死。虽然ROS的一些间接影响已为人所知,但技术上的限制意味着细胞氧化还原环境对蛋白质的直接影响仍不太清楚。一些研究小组最近的工作表明,ROS可以通过不同的修饰直接改变信号蛋白,例如通过亚硝基化、羰基化、二硫键形成和谷胱甘肽化。这些修饰调节蛋白质的活性,最近的几篇论文已经证明了它们在细胞信号事件中的重要性,特别是那些涉及细胞死亡/存活的事件。蛋白质的氧化还原修饰能够进一步调节细胞信号通路以响应细胞环境。了解它们对于我们按照自身需求调节细胞通路可能至关重要,比如在对癌细胞进行细胞毒性药物治疗时。由氧化应激介导的蛋白质修饰可以通过特定的蛋白质修饰调节信号通路,或者通过氧化蛋白质的普遍增加导致细胞功能降低,从而调节细胞凋亡。本综述讨论了蛋白质的直接氧化修饰及其对细胞凋亡的影响。

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