内皮细胞及平滑肌细胞氧化应激时Nrf2ARE对抗氧化基因表达的调控 及动脉粥样硬化及先兆子痫的关系.pdfVIP

Acta Physiologica Sinica , April 25, 2007, 59 (2): 117-127 117 Brief Review Nrf2/ARE regulated antioxidant gene expression in endothelial and smooth muscle cells in oxidative stress: implications for atherosclerosis and preeclampsia 1,* 1 1 1 2 1 Giovanni E. Mann , Jörg Niehueser-Saran , Alan Watson , Ling Gao , Tetsuro Ishii , Patricia de Winter , Richard C. M. Siow1 1Cardiovascular Division, School of Medicine, King’s College London, 150 Stamford Street, London SE1 9NH, United Kingdom; 2Department of Molecular and Cellular Physiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki 305-8577, Japan Abstract: Increased generation of reactive oxygen species (ROS) in vascular diseases such as atherosclerosis, diabetes, chronic renal failure and preeclampsia readily leads to impaired endothelium-dependent relaxation and vascular injury. To counteract ROS- and electrophile-mediated injury, cells can induce a number of genes encoding phase II detoxifying enzymes and antioxidant proteins. A cis- acting transcriptional regulatory element, designated as antioxidant response element (ARE) or electrophile response element (EpRE), mediates the transcriptional activation of genes such as heme oxygenase-1, γ-glutamylcysteine synthethase, thioredoxin reductase, glutathione-S-transferase and NAD(P)H:quinone oxidoreductase. Other antioxidant enzymes such as superoxide dismutase and cata- lase and non-enzymatic scavengers such as glutathione are also involved in scavenging ROS. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a member of the Cap ‘n’ Collar family of basic region-leucine zipper (bZIP) transcription factors, plays an important role in ARE-mediated antioxidant gene expression. Kelch-like ECH-associated protein-1 (K