Melatonin prevents oxidized low-density lipoprotein-induced increase of myosin light chain kinase activation and expression in HUVEC through ERK/MAPK signal transduction
Melatonin prevents oxidized low-density lipoprotein-induced increase of myosin light chain kinase activation and expression in HUVEC through ERK/MAPK signal transduction
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DOI：
10.1111/j.1600-079x.2008.00595.x
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发表时间：
2008-10-01
影响因子：
10.3
通讯作者：
Wang, Yuan
中科院分区：
文献类型：
--
作者：
Zhu, Hua-Qing;Cheng, Xiao-Wen;Wang, Yuan
褪黑素是松果体的主要秘书产物，在预防一些涉及自由基过程的疾病方面可能有效。高胆固醇血症的发展是一个多因素过程，其中氧化低密度脂蛋白（ox-LDL）水平升高起核心作用。本研究旨在检测褪黑激素是否通过细胞外信号调节激酶(ERK)/丝裂原活化蛋白激酶（MAPK）信号转导，阻止ox- ldl诱导的人脐静脉内皮细胞（HUVECs）中肌球蛋白轻链激酶（MLCK）激活和表达的增加。体外培养HUVEC，分别用ox-LDL、褪黑激素和PD98059 （ERK的选择性抑制剂）处理。分别采用western blot、免疫组织化学、逆转录聚合酶链反应和γ -p -32-三磷酸腺苷（ATP）掺入法检测MLCK的表达、转录和活性。结果表明，在ox- ldl处理的HUVECs中，MLCK的表达和活性增加，褪黑激素和PD98059降低了MLCK的表达和活性。ox-LDL诱导的MLCK的表达和活性与ERK的磷酸化有关。这些结果首次表明，高胆固醇血症可能与MLCK的表达有关，褪黑素可以通过ERK/MAPK信号转导降低MLCK的活性。
Melatonin, the main secretary product of the pineal gland, is potentially effective in the prevention of a number of diseases in which free radical processes are involved. The development of hypercholesterolemia is a multifactorial process in which elevated oxidized low-density lipoprotein (ox-LDL) levels play a central role. The purpose of this study was to test whether melatonin prevents ox-LDL-induced increase of myosin light chain kinase (MLCK) activation and expression in human umbilical vein endothelial cells (HUVECs) through extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signal transduction. HUVEC were cultured in vitro and treated with ox-LDL, melatonin, and PD98059 (a selective inhibitor of ERK), respectively. The expression, transcription, and activity of MLCK were measured by western blot, immunohistochemistry, reverse transcription-polymerase chain reaction and gamma-P-32-adenosine triphosphate (ATP) incorporation, respectively. The results showed that the expression and activity of MLCK were increased in ox-LDL-treated HUVECs and this was decreased by melatonin and PD98059. The expression and activity of MLCK induced by ox-LDL was associated with the phosphorylation of ERK. These results indicate for the first time that hypercholesterolemia may be associated with MLCK expression and the activity which can be reduced by melatonin through ERK/MAPK signal transduction.