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

Microvasc Res. 2018 Mar:116:26-33. doi: 10.1016/j.mvr.2017.10.001. Epub 2017 Oct 16.

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 ~80min 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.

Keywords: Epithelial sodium channel (ENaC); Oxidative stress; Vascular injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Antioxidants / pharmacology
  • Cells, Cultured
  • Electric Impedance
  • Epithelial Sodium Channels / drug effects*
  • Epithelial Sodium Channels / genetics
  • Epithelial Sodium Channels / metabolism
  • Female
  • Half-Life
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Membrane Potentials / drug effects
  • Oocytes
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Ubiquitination
  • Up-Regulation
  • Xenopus

Substances

  • Antioxidants
  • Epithelial Sodium Channels
  • SCNN1G protein, human
  • Angiotensin II
  • Hydrogen Peroxide