School of Natural Sciences, University of California, Merced, California, USA.
Ann N Y Acad Sci. 2010 Aug;1203:35-44. doi: 10.1111/j.1749-6632.2010.05551.x.
Signaling by H(2)O(2), alpha,beta-unsaturated aldehydes, such as 4-hydroxy-2-nonenal (HNE) and related chemical species, is thought to differ from signaling by other second messengers because the oxidants and other electrophiles can readily undergo nonenzymatic reactions and are therefore classified as "reactive." This brief review will describe how and when the chemistry of signaling is similar or differs from classic second messengers, such as cyclic AMP, or posttranslational signaling, such as farnesylation or ubiquitination. The chemistry of cysteine provides a common factor that underlies signaling by H(2)O(2) and HNE. Nonetheless, as H(2)O(2) and HNE are rapidly metabolized in vivo, spatial considerations are extremely important in their actions. Therefore, the locations of sources of H(2)O(2) and alpha,beta-unsaturated aldehydes, the NADPH oxidases, mitochondria, membrane lipids, and redox cycling toxicants, as well as their targets, are key factors. The activation of the JNK pathway by HNE and endogenously generated H(2)O(2) illustrates these principles.
H₂O₂、α,β-不饱和醛（如 4-羟基-2-壬烯醛（HNE）和相关化学物质）的信号转导被认为与其他第二信使的信号转导不同，因为氧化剂和其他亲电试剂可以轻易地发生非酶反应，因此被归类为“反应性”。这篇简短的综述将描述信号转导的化学与经典第二信使（如 cAMP）或翻译后信号转导（如法呢化或泛素化）的相似之处和不同之处，以及何时存在这些相似之处和不同之处。半胱氨酸的化学为 H₂O₂和 HNE 的信号转导提供了一个共同的基础。尽管如此，由于 H₂O₂和 HNE 在体内迅速代谢，因此在它们的作用中，空间考虑因素极为重要。因此，H₂O₂和α,β-不饱和醛、NADPH 氧化酶、线粒体、膜脂质和氧化还原循环毒物的来源位置及其靶标是关键因素。HNE 和内源性产生的 H₂O₂激活 JNK 途径说明了这些原则。
