Premium
Role of Ca 2+ /Calmodulin‐dependent Protein Kinase II (CaMKII) in Endothelial Cells
Author(s) -
Wang Zhen,
Ginnan Roman G.,
Singer Harold A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.637.2
Subject(s) - angiogenesis , thrombin , gene isoform , umbilical vein , calmodulin , microbiology and biotechnology , chemistry , kinase , endothelial stem cell , intracellular , vascular endothelial growth factor , biology , biochemistry , immunology , cancer research , in vitro , platelet , vegf receptors , gene , enzyme
Endothelial cell (EC) barrier function and angiogenesis are partially dependent upon increases of intracellular free Ca 2+ through G‐protein coupled receptor (GPCR) agonists such as thrombin and vascular endothelial growth factor (VEGF). The goal of these studies is to fully characterize the endogenous CaMKII isoform(s) in endothelial cells, and to test the hypothesis that the multifunctional Ca 2+ /calmodulin‐dependent serine/threonine protein kinase II (CaMKII), responds to thrombin‐ and VEGF‐stimulated Ca 2+ signals and regulates EC barrier function and angiogenesis. For the 1 st time, by RT‐PCR and western blotting, we successfully characterized the predominant CaMKII isoform expressed in cultured human umbilical vein endothelial cells (HUVEC) is the delta 6 (δ 6 ) isoform, a novel δ‐isoform lacking the 21aa c‐terminal domain. We utilized siRNA approach to suppress CaMKIIδ 6 protein expression and found it attenuated, only low dose (2.5nM) but not high dose (10nM), of thrombin‐induced increase of EC permeability. These data suggest a role of CaMKIIδ 6 in mediating changes in barrier function in response to physiological relevant doses of thrombin. By using the same approach, we found that CaMKIIδ 6 is pivotal in regulating VEGF induced HUVEC migration through Boyden Chamber. This work was supported by NIH grant to H.A.S (R01 HL‐049426).Grant Funding Source NIH grant to H.A.S (R01 HL‐049426).