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Ox‐LDL‐induced LOX‐1 expression in vascular smooth muscle cells: role of reactive oxygen species
Author(s) -
Sun Yiyi,
Chen Xiuping
Publication year - 2011
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2010.00885.x
Subject(s) - apocynin , reactive oxygen species , vascular smooth muscle , chemistry , intracellular , nadph oxidase , rotenone , nf κb , biochemistry , microbiology and biotechnology , signal transduction , pharmacology , biology , endocrinology , mitochondrion , smooth muscle
Oxidized low density lipoprotein (ox‐LDL) and lectin‐like oxidized low density lipoprotein receptor‐1 (LOX‐1) have been implicated in the development of atherosclerosis. This study was designed to investigate the expression regulation of LOX‐1 by ox‐LDL and the potential underlying mechanisms in cultured rat vascular smooth muscle cells (VSMCs). VSMCs were treated with ox‐LDL, and the expressions of LOX‐1 mRNA and proteins were determined by RT‐PCR and western blotting, respectively. The intracellular reactive oxygen species (ROS) production was monitored by flow cytometry with fluorescence probe, DCFH 2 ‐DA. The effect of several inhibitors including aspirin, NDGA, allopurinol, apocynin, and rotenone on ox‐LDL‐induced ROS formation and LOX‐1 expression was also investigated. The roles of NF‐κB p65 and JNK were explored. Ox‐LDL significantly induced LOX‐1 expression at both mRNA and protein levels in a dose‐dependent and time‐dependent manner. Aspirin, NDGA, and preconditioned apocynin suppressed ox‐LDL‐induced intracellular ROS production and LOX‐1 expression, while allopurinol and rotenone failed to do so. Vitamin C and N‐acetyl‐ l ‐cysteine demonstrated similar effect. Furthermore, both NF‐κB p65 expression and phosphorylated JNK ( p ‐JNK) to JNK expression ratio were elevated after ox‐LDL treatment. In addition, the NF‐κB inhibitor PDTC and JNK inhibitor SP600125 pretreatment partly abolished ox‐LDL‐induced LOX‐1 expression. These findings suggested that ROS mediated ox‐LDL‐induced LOX‐1 expression in VSMCs through NF‐κB and JNK signaling pathways.