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Lycopene inhibits cyclic strain‐induced endothelin‐1 expression through the suppression of reactive oxygen species generation and induction of heme oxygenase‐1 in human umbilical vein endothelial cells
Author(s) -
Sung LiChin,
Chao HungHsing,
Chen ChengHsien,
Tsai JenChen,
Liu JuChi,
Hong HongJye,
Cheng TzuHurng,
Chen JinJer
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12412
Subject(s) - lycopene , heme oxygenase , umbilical vein , reactive oxygen species , endothelin 1 , signal transduction , protein kinase b , biochemistry , heme , mapk/erk pathway , nadph oxidase , biology , chemistry , microbiology and biotechnology , antioxidant , enzyme , in vitro , receptor
Summary Lycopene is the most potent active antioxidant among the major carotenoids, and its use has been associated with a reduced risk for cardiovascular disease ( CVD ). Endothelin‐1 ( ET ‐1) is a powerful vasopressor synthesized by endothelial cells and plays a crucial role in the pathophysiology of CVD . However, the direct effects of lycopene on vascular endothelial cells have not been fully described. This study investigated the effects of lycopene on cyclic strain‐induced ET ‐1 gene expression in human umbilical vein endothelial cells ( HUVEC s) and identified the signal transduction pathways that are involved in this process. Cultured HUVEC s were exposed to cyclic strain (20% in length, 1 Hz) in the presence or absence of lycopene. Lycopene inhibited strain‐induced ET ‐1 expression through the suppression of reactive oxygen species ( ROS ) generation through attenuation of p22 phox mRNA expression and NAD (P)H oxidase activity. Furthermore, lycopene inhibited strain‐induced ET ‐1 secretion by reducing ROS ‐mediated extrace‐llular signal‐regulated kinase ( ERK ) phosphorylation. Conversely, lycopene treatment enhanced heme oxygenase‐1 ( HO ‐1) gene expression through the activation of phosphoinositide 3‐kinase ( PI 3K)/Akt pathway, followed by induction of the nuclear factor erythroid 2‐related factor 2 (Nrf2) nuclear translocation; in addition, HO ‐1 silencing partially inhibited the repressive effects of lycopene on strain‐induced ET ‐1 expression. In summary, our study showed, for the first time, that lycopene inhibits cyclic strain‐induced ET ‐1 gene expression through the suppression of ROS generation and induction of HO ‐1 in HUVEC s. Therefore, this study provides new valuable insight into the molecular pathways that may contribute to the proposed beneficial effects of lycopene on the cardiovascular system.