United States Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705, USA.
Domest Anim Endocrinol. 2012 Aug;43(2):132-45. doi: 10.1016/j.domaniend.2012.04.006. Epub 2012 May 10.
Recent advances in genome analysis and biochemical pathway mapping have advanced our understanding of how biological systems have evolved over time. Protein and DNA marker comparisons suggest that several of these systems are both ancient in origin but highly conserved into today's evolved species. However, remnants of some of the more ancient functions of these chemical systems can run in conflict with the functions that those same pathways serve in complex organisms and tissue systems today. Relevant to the present topic, nitric oxide (NO) and superoxide anion (O(2)(•-)), ancient cellular molecules in evolutionary terms, are recognized today as both necessary for the well-being and stable health of cells but also injurious to cells as elaborated in conjunction with the cellular stress response. Why the dichotomy? This question underlies one of the basic issues challenging researchers as well as practitioners in their approach to disease management. The fundamental proinflammatory response of the innate immune system of the host is needed for pathogen control but can be injurious to tissues from "collateral damage" from NO- and O(2)(•-)-derived reactive molecules capable of affecting protein function via post-translational chemical modification. This review highlights newer aspects of the biochemistry of the NO- and O(2)(•-)-mediated innate proinflammatory response and further show how protein and tissue damage via overproduction of reactive nitrogen and oxygen intermediary molecules such as peroxynitrite (ONOO(-)) might be targeted to specific epitopes of proteins. Changes in the regulation of metabolism in response to proinflammatory disease states are discussed for GH signal transduction and tissue specificity.
近年来，基因组分析和生化途径图谱的进展提高了我们对生物系统随时间进化的理解。蛋白质和 DNA 标记物的比较表明，其中一些系统的起源既古老又高度保守到今天的进化物种。然而，这些化学系统的一些更古老功能的残余部分可能与这些相同途径在复杂生物和组织系统中所服务的功能相冲突。与当前主题相关的是，一氧化氮 (NO) 和超氧阴离子 (O(2)(•-))，从进化角度来看是古老的细胞分子，今天被认为既是细胞健康和稳定所必需的，也是细胞损伤的原因，这与细胞应激反应有关。为什么会出现这种二分法？这个问题是挑战研究人员和疾病管理从业者的基本问题之一。宿主先天免疫系统的基本炎症反应对于病原体控制是必要的，但可能会对组织造成“附带损伤”，因为 NO 和 O(2)(•-)-衍生的反应性分子能够通过翻译后化学修饰影响蛋白质功能。这篇综述强调了 NO 和 O(2)(•-)-介导的先天炎症反应的生物化学的新方面，并进一步展示了如何通过过度产生反应性氮和氧中间分子（如过氧亚硝酸盐 (ONOO(-)))来靶向蛋白质的特定表位来导致蛋白质和组织损伤。还讨论了 GH 信号转导和组织特异性对炎症性疾病状态的代谢调节变化。
