Internalization and Transportation of Endothelial Cell Surface KCa2.3 and KCa3.1 in Normal Pregnancy and Preeclampsia

Shinkyu Choi, Ji Aee Kim, Seikwan Oh, Mi Hye Park, Geum Joon Cho, Suk Hyo Suh

Research output: Contribution to journalArticle

Abstract

Altered redox state modulates the expression levels of endothelial KCa2.3 and KCa3.1 (KCas) in normal pregnancy (NP) and preeclampsia (PE), thereby regulating vascular contractility. The mechanisms underlying KCas endocytosis and transportation remain unknown. We investigated the regulation of KCas 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 KCas and reduced caveolin-1 and clathrin levels. PE serum, oxidized LDL, or LPC reduced PM levels of KCas and elevated caveolin-1, clathrin, Rab5c, and early endosome antigen-1 (EEA1) levels. Reduced KCas 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 KCas levels and reduced caveolin-1 and clathrin levels. Elevated KCa2.3 levels upon catalase and GPX1 knockdown were reversed by PEG-catalase treatment. An H2O2 donor reduced clathrin and Rab5c. In contrast, elevated clathrin, caveolin-1, or colocalization of caveolin-1 with KCa3.1 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 KCas 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 H2O2-mediated pathways in NP and may be accelerated via superoxide-mediated pathways in PE.

Original languageEnglish
Article number5820839
JournalOxidative Medicine and Cellular Longevity
Volume2019
DOIs
Publication statusPublished - 2019

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Cell Biology

Fingerprint Dive into the research topics of 'Internalization and Transportation of Endothelial Cell Surface K<sub>Ca</sub>2.3 and K<sub>Ca</sub>3.1 in Normal Pregnancy and Preeclampsia'. Together they form a unique fingerprint.

  • Cite this