title: Epigallocatechin-3-gallate protects HUVECs from PM2.5-induced oxidative stress injury by activating critical antioxidant pathways.
abstract: Endothelial dysfunction and oxidative stress likely play roles in PM2.5-induced harmful effects. Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, is a potent antioxidant that exerts protective effects on cardiovascular diseases (CVDs) in part by scavenging free radicals. The exposure to ambient fine particulate matter (PM2.5) is responsible for certain CVDs. The aim of the present study was to investigate whether EGCG could also inhibit PM2.5-induced oxidative stress by activating the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in human umbilical vein endothelial cells (HUVECs). PM2.5 (200 μg/mL) increased both cell death and intracellular ROS levels significantly, whereas EGCG (50-400 μM) inhibited these effects in a concentration-dependent manner. Western blotting and PCR demonstrated that EGCG increased Nrf2 and HO-1 expression in HUVECs that had been exposed to PM2.5. PD98059 (a selective inhibitor of extracellular signal regulated kinase [ERK]-1/2) and SB203580 (a selective inhibitor of p38 MAPK), but not SP600125 (a selective inhibitor of c-jun N-terminal kinase [JNK]), attenuated the EGCG-induced Nrf2 and HO-1 expression. In addition, silencing Nrf2 abolished EGCG-induced Nrf2 and HO-1 upregulation and enhancement of cell viability. The present study suggests that EGCG protects HUVECs from PM2.5-induced oxidative stress injury by upregulating Nrf2/HO-1 via activation of the p38 MAPK and the ERK1/2 signaling pathways.
authors: The Fist Clinical Hospital, Shanxi Medical University, 56 Xinjiannanlu, Taiyuan, Shanxi 030001, China. ygzloveqq@126.com.
authors: Guang-Zhao
authors: GZ
authors: Yang
authors: Department of Pharmacology, Shanxi Medical University, 56 Xinjiannanlu, Taiyuan, Shanxi 030001, China. wzhaojun1025@126.com.|Department of Physiology, Shanxi Province Key Laboratory of Cellular Physiology, Shanxi Medical University, 56 Xinjiannanlu, Taiyuan, Shanxi 030001, China. wzhaojun1025@126.com.
authors: Zhao-Jun
authors: ZJ
authors: Wang
authors: The Fist Clinical Hospital, Shanxi Medical University, 56 Xinjiannanlu, Taiyuan, Shanxi 030001, China. pinkbai@163.com.
authors: Feng
authors: F
authors: Bai
authors: Department of Pharmacology, Shanxi Medical University, 56 Xinjiannanlu, Taiyuan, Shanxi 030001, China. sxykdxyxy@163.com.
authors: Xiao-Jiang
authors: XJ
authors: Qin
authors: The Fist Clinical Hospital, Shanxi Medical University, 56 Xinjiannanlu, Taiyuan, Shanxi 030001, China. 13834691242@163.com.
authors: Jing
authors: J
authors: Cao
authors: The Fist Clinical Hospital, Shanxi Medical University, 56 Xinjiannanlu, Taiyuan, Shanxi 030001, China. lvjiyuan11@163.com.
authors: Ji-Yuan
authors: JY
authors: Lv
authors: Department of Pharmacology, Shanxi Medical University, 56 Xinjiannanlu, Taiyuan, Shanxi 030001, China. zmspharmacol@sohu.com.|Department of Physiology, Shanxi Province Key Laboratory of Cellular Physiology, Shanxi Medical University, 56 Xinjiannanlu, Taiyuan, Shanxi 030001, China. zmspharmacol@sohu.com.
authors: Ming-Sheng
authors: MS
authors: Zhang
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D052638:Particulate Matter / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D002392:Catechin; C045651:epigallocatechin gallate; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases