Oxidized low-density lipoprotein attenuated desmoglein 1 and desmocollin 2 expression via LOX-1/Ca(2+)/PKC-β signal in human umbilical vein endothelial cells.
Numerous studies have reported the presence of oxidized LDL (ox-LDL) and expression of its lectin-like receptor, LOX-1, have been shown in atherosclerotic regions. The present study aims to investigate the effects of ox-LDL on expression of desmoglein 1 (DSG1) and desmocollin 2 (DSC2) in endothelial cells, and to explore the role of LOX-1 mediated signal in the permeability injury associated with DSG1 and DSC2 disruption induced by oxidized lipoprotein. RT-PCR and Western blotting were applied to determine the mRNA and protein expression levels of DSG1 and DSC2 in human umbilical vein endothelial cells (HUVECs) respectively. Immunoreactivities of DSG1 and DSC2 were detected by laser scanning confocal microscope (LSCM). HUVEC monolayers permeability was evaluated by FITC-labeled LDL in transwell assay system. The possible signal was assessed using in vitro blocking LOX-1 or Ca(2+) channel or PKC. The DSG1 and DSC2 expression were decreased by ox-LDL in concentration- and time-dependent manner. The effects of ox-LDL were mediated by its endothelial receptor, LOX-1. In parallel experiments, ox-LDL increased the influx of extracellular calcium, activation of protein kinase C (PKC) and permeability to LDL, which was inhibited by the LOX-1blocking antibody (10 μg/ml), Ca(2+) channel blocker (Diltiazem, 50 μmol/L) and PKC-β inhibitor (hispidin, 4 μmol/L). These results suggested that ox-LDL-induced decrease in DSG1 and DSC2 expression and monolayer barrier injury via calcium uptake and PKC-β activation following up-regulation of LOX-1 is one of the mechanisms of inducing greater permeability in HUVECs.
Department of Basic Medical, Hunan Traditional Chinese Medical College, Zhuzhou, Hunan 412000, China.
Yuan-Bin
YB
Li
Clinical Research Institution, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
Qing-Hai
QH
Zhang
Department of Basic Medical, Hunan Traditional Chinese Medical College, Zhuzhou, Hunan 412000, China.
Zhuang
Z
Chen
Department of Basic Medical, Hunan Traditional Chinese Medical College, Zhuzhou, Hunan 412000, China.
Zhi-Jun
ZJ
He
Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China. Electronic address: ghyi6108@163.com.
Guang-Hui
GH
Yi
D002118:Calcium / Q000378:metabolism; D002199:Capillary Permeability; D051187:Desmocollins / Q000235:genetics*; D051183:Desmoglein 1 / Q000235:genetics*; D003896:Desmosomes / Q000378:metabolism; D015536:Down-Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D064546:Protein Kinase C beta / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015398:Signal Transduction
C081561:DSC2 protein, human; D051187:Desmocollins; D051183:Desmoglein 1; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D064546:Protein Kinase C beta; D002118:Calcium
DSC2; DSG1; Endothelium permeability; LOX-1; Ox-LDL; PKC