Differential roles of PKCalpha and PKCvarepsilon in controlling the gene expression of Nox4 in human endothelial cells.

Differential roles of PKCalpha and PKCvarepsilon in controlling the gene expression of Nox4 in human endothelial cells. Research Abstract Details 

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Differential roles of PKCalpha and PKCvarepsilon in controlling the gene expression of Nox4 in human endothelial cells. Abstract Text:

Hui Xu,Claudia Goettsch,Ning Xia,Sven Horke,Henning Morawietz,Ulrich ,Huige Li,

NADPH oxidases are major sources of superoxide in the vascular wall. This study investigates the role of protein kinase C (PKC) in regulating gene expression of NADPH oxidases. Treatment of human umbilical vein endothelial cells (HUVEC) and HUVEC-derived EA.hy 926 endothelial cells with phorbol 12-myristate 13-acetate (PMA) or phorbol 12,13-dibutyrate led to a PKC-dependent biphasic expression of the gp91phox homolog Nox4. A downregulation of Nox4 was observed at 6 h and an upregulation at 48 h after phorbol ester treatment. The early Nox4 downregulation was associated with a reduced superoxide production, whereas the late Nox4 upregulation was accompanied by a clear enhancement of superoxide. PMA activated the PKC isoforms alpha and varepsilon in HUVEC and EA.hy 926 cells. Knockdown of PKCvarepsilon by siRNA prevented the early downregulation of Nox4, whereas knockdown of PKCalpha selectively abolished the late Nox4 upregulation. Vascular endothelial growth factor (VEGF), which activates PKCalpha but not PKCvarepsilon in HUVEC, increased Nox4 expression without the initial downregulation. VEGF-induced Nox4 upregulation was associated with an enhanced proliferation and angiogenesis of HUVEC. Both effects could be reduced by inhibition of NADPH oxidase. Thus, a selective inhibition/knockdown of PKCalpha may represent a novel therapeutic strategy for vascular disease.

Differential roles of PKCalpha and PKCvarepsilon in controlling the gene expression of Nox4 in human endothelial cells. Publishing Authors By Initials

H Xu,C Goettsch,N Xia,S Horke,H Morawietz,U ,H Li,

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Differential roles of PKCalpha and PKCvarepsilon in controlling the gene expression of Nox4 in human endothelial cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Free radical biology & medicine

VOLUME: 44

Page Numbers: 1656-67

Journal Abbreviation: Free Radic. Biol. Med.

ISSN: 0891-5849

DAY: 7

MONTH: 02

YEAR: 2008

Differential roles of PKCalpha and PKCvarepsilon in controlling the gene expression of Nox4 in human endothelial cells. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Differential roles of PKCalpha and PKCvarepsilon in controlling the gene expression of Nox4 in human endothelial cells.

AFFILIATION: Department of Pharmacology, Johannes Gutenberg University, D-55131 Mainz, Germany; Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Country: United States

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MEDLINETA: Free Radic Biol Med

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