Green tea polyphenols down-regulate caveolin-1 expression via ERK1/2 and p38MAPK in endothelial cells.
Caveolin-1 (Cav-1), a negative regulator of endothelial nitric oxide synthase (eNOS), influences various aspects of the cardiovascular functions. We had reported that a high-fat diet up-regulated aortic Cav-1 expressions in rats. In this study, we investigated the effects of green tea polyphenols (GTPs) on endothelial Cav-1 expression and phosphorylation in vitro. Bovine aortic endothelial cells (BAECs) were treated with 4 microg/ml GTPs for 0, 4, 8, 12, 16 and 24 h, and with 0, 0.04, 0.4, 4 and 40 microg/ml GTPs for 16 h, respectively. Cav-1 protein and mRNA were detected using Western blot and reverse transcriptase polymerase chain reaction. Cav-1 protein expression was down-regulated after treatment of BAECs with 4 microg/ml GTPs for 12, 16 and 24 h. And decrease in the level of Cav-1 mRNA was observed after GTP treatment for 4 and 8 h. GTPs (0.04-4 microg/ml) down-regulate Cav-1 protein expressions and mRNA levels dose dependently. PD98059, an inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2), up-regulated Cav-1 expression in BAECs alone and abolished the down-regulation effects of GTPs in BAECs while pretreatment with it. Inhibition of p38 mitogen-activated protein kinase (p38MAPK) with SB203580, which down-regulates Cav-1 expression in BAECs alone, deteriorated the Cav-1 down-regulating effects by GTPs. In addition to the effects on expression of Cav-1, GTP treatment inhibited phosphorylation of Cav-1 [tyrosine 14 (Tyr14)]. These data indicate that GTPs down-regulate gene expression of Cav-1 time- and dose- dependently via activating ERK1/2 and inhibiting p38MAPK signaling.
Li
Yanrong
Y
Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Ying
Chenjiang
C
Zuo
Xuezhi
X
Yi
Haiwei
H
Yi
Weijie
W
Meng
Yi
Y
Ikeda
Katsumi
K
Ye
Xiaolei
X
Yamori
Yukio
Y
Sun
Xiufa
X
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D051242:Caveolin 1 / Q000096:biosynthesis*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048370:MAP Kinase Kinase 2 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013662:Tea / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D051242:Caveolin 1; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D052250:Nitric Oxide Synthase Type III; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048370:MAP Kinase Kinase 2; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one