In:
Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2019 ( 2019-11-23), p. 1-13
Abstract:
Altered redox state modulates the expression levels of endothelial K Ca 2.3 and K Ca 3.1 (K Ca s) in normal pregnancy (NP) and preeclampsia (PE), thereby regulating vascular contractility. The mechanisms underlying K Ca s endocytosis and transportation remain unknown. We investigated the regulation of K Ca s expression in plasma membrane (PM) during NP and PE. Cultured human uterine artery endothelial cells were incubated in serum from normal nonpregnant women and women with NP or PE, or in oxidized LDL-, or lysophosphatidylcholine- (LPC-) containing a medium for 24 hours. NP serum elevated PM levels of K Ca s and reduced caveolin-1 and clathrin levels. PE serum, oxidized LDL, or LPC reduced PM levels of K Ca s and elevated caveolin-1, clathrin, Rab5c, and early endosome antigen-1 (EEA1) levels. Reduced K Ca s levels by PE serum or LPC were reversed by inhibition of caveolin-1, clathrin, or EEA1. Catalase and glutathione peroxidase 1 (GPX1) knockdown elevated PM-localized K Ca s levels and reduced caveolin-1 and clathrin levels. Elevated K Ca 2.3 levels upon catalase and GPX1 knockdown were reversed by PEG-catalase treatment. An H 2 O 2 donor reduced clathrin and Rab5c. In contrast, elevated clathrin, caveolin-1, or colocalization of caveolin-1 with K Ca 3.1 by PE serum or LPC was reversed by NADPH oxidase inhibitors or antioxidants. A superoxide donor xanthine+xanthine oxidase elevated caveolin-1 or Rab5c levels. We concluded that K Ca s are endocytosed in a caveola- or a clathrin-dependent manner and transported in a Rab5c- and EEA1-dependent manner during pregnancy. The endocytosis and transportation processes may slow down via H 2 O 2 -mediated pathways in NP and may be accelerated via superoxide-mediated pathways in PE.
Type of Medium:
Online Resource
ISSN:
1942-0900
,
1942-0994
DOI:
10.1155/2019/5820839
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2019
detail.hit.zdb_id:
2455981-7
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