Ceaser E K, Moellering D R, Shiva S, Ramachandran A, Landar A, Venkartraman A, Crawford J, Patel R, Dickinson D A, Ulasova E, Ji S, Darley-Usmar V M
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, AL 35294-2180, USA.
Biochem Soc Trans. 2004 Feb;32(Pt 1):151-5. doi: 10.1042/bst0320151.
Cellular redox signalling is mediated by the post-translational modification of proteins by reactive oxygen/nitrogen species or the products derived from their reactions. In the case of oxidized lipids, several receptor-dependent and -independent mechanisms are now emerging. At low concentrations, adaptation to oxidative stress in the vasculature appears to be mediated by induction of antioxidant defences, including the synthesis of the intracellular antioxidant glutathione. At high concentrations apoptosis occurs through mechanisms that have yet to be defined in detail. Recent studies have revealed a mechanism through which electrophilic lipids, formed as the reaction products of oxidation, orchestrate these adaptive responses in the vasculature. Using a proteomics approach, we have identified a subset of proteins in cells that we term the electrophile-responsive proteome. Electrophilic modification of thiol groups in these proteins can initiate cell signalling events through the transcriptional activation of genes regulated by consensus sequences for the antioxidant response element found in their promoter regions. The insights gained from our understanding of the biology of these mechanisms will be discussed in the context of cardiovascular disease.
细胞氧化还原信号传导是由活性氧/氮物种或其反应衍生产物对蛋白质进行的翻译后修饰介导的。就氧化脂质而言，目前正在出现几种受体依赖性和非依赖性机制。在低浓度下，血管系统对氧化应激的适应似乎是由抗氧化防御的诱导介导的，包括细胞内抗氧化剂谷胱甘肽的合成。在高浓度下，细胞凋亡通过尚未详细定义的机制发生。最近的研究揭示了一种机制，通过该机制，作为氧化反应产物形成的亲电脂质在血管系统中协调这些适应性反应。使用蛋白质组学方法，我们在细胞中鉴定出了一组蛋白质，我们将其称为亲电反应蛋白质组。这些蛋白质中硫醇基团的亲电修饰可通过其启动子区域中发现的抗氧化反应元件共有序列调控的基因的转录激活来引发细胞信号事件。我们将在心血管疾病的背景下讨论从对这些机制生物学的理解中获得的见解。
