Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University, Atlanta, GA 30322, USA.
Crit Rev Biochem Mol Biol. 2013 Mar-Apr;48(2):173-81. doi: 10.3109/10409238.2013.764840. Epub 2013 Jan 29.
Rapid advances in redox systems biology are creating new opportunities to understand complexities of human disease and contributions of environmental exposures. New understanding of thiol-disulfide systems have occurred during the past decade as a consequence of the discoveries that thiol and disulfide systems are maintained in kinetically controlled steady states displaced from thermodynamic equilibrium, that a widely distributed family of NADPH oxidases produces oxidants that function in cell signaling and that a family of peroxiredoxins utilize thioredoxin as a reductant to complement the well-studied glutathione antioxidant system for peroxide elimination and redox regulation. This review focuses on thiol/disulfide redox state in biologic systems and the knowledge base available to support development of integrated redox systems biology models to better understand the function and dysfunction of thiol-disulfide redox systems. In particular, central principles have emerged concerning redox compartmentalization and utility of thiol/disulfide redox measures as indicators of physiologic function. Advances in redox proteomics show that, in addition to functioning in protein active sites and cell signaling, cysteine residues also serve as redox sensors to integrate biologic functions. These advances provide a framework for translation of redox systems biology concepts to practical use in understanding and treating human disease. Biological responses to cadmium, a widespread environmental agent, are used to illustrate the utility of these advances to the understanding of complex pleiotropic toxicities.
氧化还原系统生物学的快速发展为理解人类疾病的复杂性和环境暴露的贡献提供了新的机会。在过去的十年中，由于发现硫醇和二硫键系统处于动力学控制的稳定状态，与热力学平衡相偏离，广泛分布的 NADPH 氧化酶家族产生的氧化剂在细胞信号转导中发挥作用，以及一族过氧化物酶利用硫氧还蛋白作为还原剂来补充研究充分的谷胱甘肽抗氧化系统，用于过氧化物消除和氧化还原调节，因此对硫醇-二硫键系统有了新的认识。本文重点介绍生物系统中的硫醇/二硫键氧化还原状态，以及支持开发综合氧化还原系统生物学模型的知识库，以更好地理解硫醇-二硫键氧化还原系统的功能和功能障碍。特别是，关于氧化还原区室化和硫醇/二硫键氧化还原测量作为生理功能指标的实用性的核心原则已经出现。氧化还原蛋白质组学的进展表明，除了在蛋白质活性位点和细胞信号转导中发挥作用外，半胱氨酸残基还作为氧化还原传感器，整合生物功能。这些进展为将氧化还原系统生物学概念转化为理解和治疗人类疾病的实际应用提供了框架。镉（一种广泛存在的环境剂）对生物的响应被用来举例说明这些进展对理解复杂的多效毒性的实用性。
