硫氧还蛋白与氧化还原反应

硫氧还蛋白是生物体调节体内氧化还原系统的一种重要蛋白质,它参与了生物体内众多的氧化还原反应,其活性位点是-Cys-Gly-Pro-Cys-,在众多的生命过程中,通过构象的改变行使其调节功能。     

氧化还原与细胞凋亡的关联

细胞内氧化还原状态与细胞凋亡相互关联的机理仍然存在很大争议。细胞内氧化还原状态的改变促进了氧自由基(ROS)的产生和凋亡诱导因子的激活,致使细胞凋亡的同时又加剧了细胞内氧化还原状态的改变。通过激活细胞凋亡信号激酶(ASK-1)、氧化还原转录因子NF-κB、AP-1及Caspase激活,揭示了细胞内氧化还原状态伴随细胞凋亡的不同阶段。     

Redox signaling

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have recently been shown to be involved in a multiplicity of physiological responses through modulation of signaling pathways. Some of the specific signaling components altered by reactive oxygen and nitrogen species (RONS) have begun to be identified. We will discuss RONS signaling by detailing the chemistry of signaling, the roles of antioxidant enzymes as signaling components, thiol chemistry in the specificity of RONS signaling, NO-heme interactions, and some do's and don'ts of redox signal research. The principal points raised are that: (1) as with classic signaling pathways, signaling by RONS is regulated; (2) antioxidant enzymes are essential 'turn-off' components in signaling; (3) spatial relationships are probably more important in RONS signaling than the overall 'redox state' of the cell; (4) deprotonation of cysteines to form the thiolate, which can react with RONS, occurs in specific protein sites providing specificity in signaling; (5) although multiple chemical mechanisms exist for producing nitrosothiols, their formation in vivo remains unclear; and (6) caution should be taken in the use of 'antioxidants' in signal transduction.     

Redox imbalance

Substantial evidence implies that redox imbalance attributable to an overproduction of reactive oxygen species or reactive nitrogen species that overwhelm the protective defense mechanism of cells contributes to all forms of Parkinsons disease. Factors such as dopamine, neuromelanin, and transition metals may, under certain circumstances, contribute to the formation of oxygen species such as H₂O₂, superoxide radicals, and hydroxyl radicals and react with reactive nitrogen species such as nitric oxide or peroxinitrite. Mitochodrial dysfunction and excitotoxicity may be a cause and a result of oxidative stress. Consequences of this redox imbalance are lipid peroxidation, oxidation of proteins, DNA damage, and interference of reactive oxygen species with signal transduction pathways. These consequences become even more harmful when genetic variations impair the normal degradation of altered proteins. Therefore, therapeutic strategies must aim at reducing free-radical formation and scavenging free-radicals.     

Redox signaling

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have recently been shown to be involved in a multiplicity of physiological responses through modulation of signaling pathways. Some of the specific signaling components altered by reactive oxygen and nitrogen species (RONS) have begun to be identified. We will discuss RONS signaling by detailing the chemistry of signaling, the roles of antioxidant enzymes as signaling components, thiol chemistry in the specificity of RONS signaling, .NO-heme interactions, and some do's and don'ts of redox signal research. The principal points raised are that: (1) as with classic signaling pathways, signaling by RONS is regulated; (2) antioxidant enzymes are essential 'turn-off components in signaling; (3) spatial relationships are probably more important in RONS signaling than the overall 'redox state' of the cell; (4) deprotonation of cysteines to form the thiolate, which can react with RONS, occurs in specific protein sites providing specificity in signaling; (5) although multiple chemical mechanisms exist for producing nitrosothiols, their formation in vivo remains unclear; and (6) caution should be taken in the use of 'antioxidants' in signal transduction.     

Redox proteomics and drug development

As alterations of the redox homeostasis lie at the root of many pathophysiological processes in human health, redox proteomics holds the promise to shed further light on fundamental biological processes. In this review, the mechanisms of reactive oxygen species (ROS) and reactive nitrogen species (RNS) production are reviewed, mainly addressing those chemical phenomena which have already been associated with pathological conditions (of the central nervous system, cardiovascular system, or simply related to aging and altered-cell cycle regulation). From Alzheimer's to Parkinson's and Hungtinton's disease, from ageing to cancer, oxidative stress (OS) appears to represent a common trait in so many relevant biological aspects of human health, that further investments in the field of redox proteomics ought to be mandatory. For the foreseeable future, redox proteomics will likely play a pivotal role in the quest for new therapeutical targets and their validation, in the process of determining OS-triggered cellular alteration upon drug treatments and thus in the very heart of the design and testing of new drugs and their metabolites against those pathologies relying on altered redox homeostasis.     

Redox signaling and cardiac sarcomeres

Oxidative stress is common in many clinically important cardiac disorders, including ischemia/reperfusion, diabetes, and hypertensive heart disease. Oxidative stress leads to derangements in pump function due to changes in the expression or function of proteins that regulate intracellular Ca(2+) homeostasis. There is growing evidence that the cardiodepressant actions of reactive oxygen species (ROS) also are attributable to ROS-dependent signaling events in the sarcomere. This minireview focuses on myofilament protein post-translational modifications induced by ROS or ROS-activated signaling enzymes that regulate cardiac contractility.     

谷胱甘肽化修饰与氧化还原信号转导

蛋白质谷胱甘肽化（S-glutathionylation）是一种重要的翻译后修饰方式,氧化还原信号转导途径的很多相关分子都可受到谷胱甘肽化的调节,尤其是一些重要的蛋白激酶和转录因子。因此蛋白质的谷胱甘肽化修饰日益引起人们的重视。人们推测,谷胱甘肽化可能是细胞内氧化还原信号转导的一种重要机制。     

The Redox Proteome

The redox proteome consists of reversible and irreversible covalent modifications that link redox metabolism to biologic structure and function. These modifications, especially of Cys, function at the molecular level in protein folding and maturation, catalytic activity, signaling, and macromolecular interactions and at the macroscopic level in control of secretion and cell shape. Interaction of the redox proteome with redox-active chemicals is central to macromolecular structure, regulation, and signaling during the life cycle and has a central role in the tolerance and adaptability to diet and environmental challenges.     

Redox loops and proton pumps

In a Review-Hypothesis, Mitchell [(1987) FEBS Lett. 222,235-245] has recently suggested possible molecular mechanisms for proton translocation by cytochrome oxidase. In describing these mechanisms, he extended his own concept of a redox loop in a manner expected to lead to confusion. He also stated that the term redox-linked proton pump implies an indirect coupling between electron transfer and proton translocation, and that this type of coupling is very difficult to test experimentally. Here it is argued that the original meaning of a redox loop should be maintained, and proper definitions of the terms redox-linked proton pump and direct or indirect coupling are formulated. In addition, it is reasoned that both types of coupling are amenable to experimental tests.     

Redox metals and neurodegenerative disease

Multiple lines of evidence implicate redox-active transition metals as mediators of oxidative stress in neurodegenerative diseases. Among the recent research discoveries is the finding that transition metals bind to proteins associated with neurodegeneration, including the prion protein. Whereas binding in the latter case may serve an antioxidant function, adventitious binding of metals to other proteins appears to preserve their catalytic redox activity in a manner that disturbs free radical homeostasis. Alterations in the levels of copper- and iron-containing metalloenzymes, involved in processing partially reduced oxygen species, are also likely to contribute to altered redox balance in neurodegenerative diseases. Nonetheless, even in familial forms of amyotrophic lateral sclerosis linked to mutations in superoxide dismutase, it is unclear whether an altered enzyme activity or, indirectly, a disturbance in transition-metal homeostasis is involved in the disease pathogenesis.     

端粒-端粒酶系统与氧化还原微环境

端粒,作为染色体末端的特殊结构,可以有效保护染色体,防止其降解、末端融合和重组。端粒酶是通过逆转录维持端粒长度的蛋白核酸复合体。二者共同构成了端粒-端粒酶系统。经过近30年的研究,人们发现该系统与人类健康密切相关。氧化应激可导致端粒结构与功能的改变。本文总结了影响端粒、端粒酶结构与功能的不同途径,并分析了氧化还原微环境和氧化应激对其的影响及对人类疾病的作用。