Melatonin prevents oxidized low-density lipoprotein-induced increase of myosin light chain kinase activation and expression in HUVEC through ERK/MAPK signal transduction.
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-(32)P-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.
Zhu
Hua-Qing
HQ
Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Ministry of Education and Anhui Province, Anhui, China.
Cheng
Xiao-Wen
XW
Xiao
Lin-Lin
LL
Jiang
Zhi-Kui
ZK
Zhou
Qing
Q
Gui
Shu-Yu
SY
Wei
Wei
W
Wang
Yuan
Y
D000704:Analysis of Variance; D000975:Antioxidants; D015153:Blotting, Western; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008550:Melatonin / Q000627:therapeutic use*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins
D000975:Antioxidants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D009219:Myosin-Light-Chain Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D008550:Melatonin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one