Green tea polyphenols down-regulate caveolin-1 expression via ERK1/2 and p38MAPK in endothelial cells

J Nutr Biochem. 2009 Dec;20(12):1021-7. doi: 10.1016/j.jnutbio.2008.12.001. Epub 2009 Feb 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cattle
  • Caveolin 1 / biosynthesis*
  • Down-Regulation
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Flavonoids / pharmacology
  • Imidazoles / pharmacology
  • MAP Kinase Kinase 2 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Nitric Oxide Synthase Type III / metabolism
  • Pyridines / pharmacology
  • RNA, Messenger / metabolism
  • Tea / chemistry
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Caveolin 1
  • Flavonoids
  • Imidazoles
  • Pyridines
  • RNA, Messenger
  • Tea
  • Catechin
  • epigallocatechin gallate
  • Nitric Oxide Synthase Type III
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 2
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one