Increased intracellular calcium transients by calmodulin antagonists differentially modulate tumor necrosis factor-alpha-induced E-selectin and ICAM-1 expression.
We investigated the role of intracellular calcium ([Ca(2+)](i)) in adhesion molecule expression in human umbilical vascular endothelial cells (HUVECs). Calmodulin (CaM) antagonists, W-7, trifluoperazine and chlorpromazine, triggered a rise in [Ca(2+)](i) in HUVECs. In the presence of extracellular Ca(2+), thapsigargin pretreatment completely prevented W-7-stimulated increase in [Ca(2+)](i), indicating that increase is attributable to the release of Ca(2+) from internal stores. The increased [Ca(2+)](i) acted as a second messenger to enhance tumor necrosis factor-alpha (TNF-alpha)-induced E-selectin and suppress intercellular cell adhesion molecule (ICAM-1) expression. Preincubation of HUVECs with the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraaceticacetomethyl ester blocked W-7-mediated effects on E-selectin and ICAM-1. The W-7 effects were paralleled by changes in the respective mRNAs, suggesting regulation at a pretranslational level. These findings indicate that CaM-regulated [Ca(2+)](i) in HUVECs may play an important role in controlling expression of endothelial adhesion molecules involved in atherogenesis.
Chen
Kuang-Hua
KH
Department of Medicine, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. kchen@niaid.nih.gov
Chang
Benny Hung-Junn
BH
Younan
Patrick
P
Shlykov
Sergiy G
SG
Sanborn
Barbara M
BM
Chan
Lawrence
L
D002118:Calcium / Q000097:blood / Q000378:metabolism*; D020013:Calcium Signaling; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002478:Cells, Cultured; D019040:E-Selectin / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D011336:Probability; D012313:RNA / Q000032:analysis; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*
D002147:Calmodulin; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D012313:RNA; D002118:Calcium