Stop the flow: a paradigm for cell signaling mediated by reactive oxygen species in the pulmonary endothelium

Annu Rev Physiol. 2012;74:403-24. doi: 10.1146/annurev-physiol-020911-153324. Epub 2011 Nov 7.

Abstract

The lung endothelium is exposed to mechanical stimuli through shear stress arising from blood flow and responds to altered shear by activation of NADPH (NOX2) to generate reactive oxygen species (ROS). This review describes the pathway for NOX2 activation and the downstream ROS-mediated signaling events on the basis of studies of isolated lungs and flow-adapted endothelial cells in vitro that are subjected to acute flow cessation (ischemia). Altered mechanical stress is detected by a cell-associated complex involving caveolae and other membrane proteins that results in endothelial cell membrane depolarization and then the activation of specific kinases that lead to the assembly of NOX2 components. ROS generated by this enzyme amplify the mechanosignal within the endothelial cell to regulate activation and/or synthesis of proteins that participate in cell growth, proliferation, differentiation, apoptosis, and vascular remodeling. These responses indicate an important role for NOX2-derived ROS associated with mechanotransduction in promoting vascular homeostasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Endothelial Cells / metabolism
  • Endothelial Cells / physiology*
  • Endothelium / metabolism
  • Endothelium / physiology*
  • Humans
  • Ion Channels / physiology
  • Lung / metabolism
  • Lung / physiology*
  • Mechanotransduction, Cellular / physiology
  • Membrane Glycoproteins / physiology
  • NADPH Oxidase 2
  • NADPH Oxidases / metabolism
  • NADPH Oxidases / physiology
  • Pulmonary Circulation / physiology
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Stress, Mechanical

Substances

  • Ion Channels
  • Membrane Glycoproteins
  • Reactive Oxygen Species
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases