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NADPH oxidase 2-derived superoxide downregulates endothelial K Ca3.1 in preeclampsia

Title
NADPH oxidase 2-derived superoxide downregulates endothelial K Ca3.1 in preeclampsia
Authors
Choi S.Kim J.A.Na H.-Y.Kim J.-E.Park S.Han K.-H.Kim Y.J.Suh S.H.
Ewha Authors
김영주서석효한기환최신규박성희
SCOPUS Author ID
김영주scopus; 서석효scopus; 한기환scopus; 최신규scopus; 박성희scopus
Issue Date
2013
Journal Title
Free Radical Biology and Medicine
ISSN
0891-5849JCR Link
Citation
vol. 57, pp. 10 - 21
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Endothelial dysfunction is associated with KCa3.1 dysfunction and contributes to the development of hypertension in preeclampsia. However, evidence of endothelial KCa3.1 dysfunction in the vascular system from women with preeclampsia is still lacking. Therefore, we examined whether endothelial KCa3.1 dysfunction occurs in vessels from women with preeclampsia. We compared KCa3.1 and NADPH oxidase (NOX) expression in umbilical vessels and primary cultured human umbilical vein endothelial cells (HUVECs) from normal (NP; n=17) and preeclamptic pregnancy (PE; n=19) and examined the effects of plasma from NP or PE on KCa3.1 and NOX2 expression in primary cultured HUVECs from NP or human uterine microvascular endothelial cells. The endothelial KCa3.1 was downregulated, and NOX2 was upregulated, in umbilical vessels and HUVECs from PE, compared with those from NP. In addition, HUVECs from PE showed a significant decrease in K Ca3.1 current. Plasma from PE induced KCa3.1 down regulation, NOX2 upregulation, phosphorylated-p38 mitogen-activated protein kinase downregulation, and superoxide generation, and these effects were prevented by antioxidants (tempol or tiron), NOX2 inhibition, or anti-lectin-like oxidized low-density lipoprotein (LDL) receptor 1 (LOX1) antibody. Oxidized LDL and the superoxide donor xanthine/xanthine oxidase mixture induced KCa3.1 downregulation. In contrast, plasma from PE did not generate hydrogen peroxide, and the hydrogen peroxide donor tert-butylhydroperoxide induced KCa3.1 upregulation. These results provide the first evidence that plasma from PE generates superoxide via a LOX1-NOX2-mediated pathway and downregulates endothelial KCa3.1, which may contribute to endothelial dysfunction and vasculopathy in preeclampsia. This suggests KCa3.1as a novel target for patients with preeclampsia. © 2012 Elsevier Inc.
DOI
10.1016/j.freeradbiomed.2012.12.009
Appears in Collections:
의과대학 > 의학과 > Journal papers
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