Angiotensin II regulates δ-ENaC in human umbilical vein endothelial cells

Charles A. Downs, Nicholle M. Johnson, Camila Coca, My N. Helms

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The amiloride-sensitive epithelial sodium channel (ENaC) has been characterized in a variety of non-epithelial tissues. In the current study we sought to understand the effect of angiotensin II on δ ENaC function using human umbilical vein endothelial cells (HUVECs). The δ ENaC subunit is found in humans, but notably absent in rat and most mouse epithelial tissues. In this study we report the presence of δ ENaC in HUVECS with a half-life of ~ 80 min and a change in δ ENaC abundance when HUVECs were treated with angiotensin II. We also observed that angiotensin II increased apical membrane expression of δ ENaC and decreased protein ubiquitination. Equivalent short circuit current measurements showed angiotensin II increased δ ENaC ion transport in HUVEC cells. Treatment with the antioxidant apocynin attenuated angiotensin II mediated effects indicating an important role for angiotensin-derived H2O2 in δ ENaC subunit regulation. Whole cell recordings from oocytes injected with δβγ ENaC shows H2O2-sensitive current. These results suggest that δ ENaC subunits can make up functional channel in HUVEC cells that are regulated by angiotensin II in a redox-sensitive manner. The novel findings have significant implications for our understanding of the role of ENaC in vascular conditions in which oxidative stress occurs.

Original languageEnglish (US)
Pages (from-to)26-33
Number of pages8
JournalMicrovascular Research
Volume116
DOIs
StatePublished - Mar 2018
Externally publishedYes

Keywords

  • Epithelial sodium channel (ENaC)
  • Oxidative stress
  • Vascular injury

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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