Type I cell ROS kinetics under hypoxia in the intact mouse carotid body ex vivo: a FRET-based study

Am J Physiol Cell Physiol. 2015 Jan 1;308(1):C61-7. doi: 10.1152/ajpcell.00370.2013. Epub 2014 Oct 15.

Abstract

Reactive oxygen species (ROS) mainly originating from NADPH oxidases have been shown to be involved in the carotid body (CB) oxygen-sensing cascade. For measuring ROS kinetics, type I cells of the mouse CB in an ex vivo preparation were transfected with the ROS sensor construct FRET-HSP33. After 2 days of tissue culture, type I cells expressed FRET-HSP33 as shown by immunohistochemistry. In one population of CBs, 5 min of hypoxia induced a significant and reversible decrease of type I cell ROS levels (n = 9 CBs; P < 0.015), which could be inhibited by 4-(2-aminoethyl)benzensulfonylfluorid (AEBSF), a highly specific inhibitor of the NADPH oxidase subunits p47(phox) and p67(phox). In another population of CBs, however, 5 min of hypoxia induced a significant and reversible increase of ROS levels in type I cells (n = 8 CBs; P < 0.05), which was slightly enhanced by administration of 3 mM AEBSF. These different ROS kinetics seemed to coincide with different mice breeding conditions. Type I cells of both populations showed a typical hypoxia-induced membrane potential (MP) depolarization, which could be inhibited by 3 mM AEBSF. ROS and MP closely followed the hypoxic decrease in CB tissue oxygen as measured with an O2-sensitive dye. We conclude that attenuated p47(phox) subunit activity of the NADPH oxidase under hypoxia is the physiological trigger for type I cell MP depolarization probably due to ROS decrease, whereas the observed ROS increase has no influence on type I cell MP kinetics under hypoxia.

Keywords: FRET-HSP33; NADPH oxidase; ROS; carotid body; hypoxia; membrane potential; tissue oxygen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Biosensing Techniques*
  • Carotid Body / drug effects
  • Carotid Body / metabolism*
  • Cell Hypoxia
  • Enzyme Inhibitors / pharmacology
  • Female
  • Fluorescence Resonance Energy Transfer*
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Heat-Shock Proteins / genetics
  • Kinetics
  • Luminescent Proteins / biosynthesis
  • Luminescent Proteins / genetics
  • Membrane Potentials
  • Mice, Inbred C57BL
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / metabolism
  • Phenotype
  • Phosphoproteins / antagonists & inhibitors
  • Phosphoproteins / metabolism
  • Reactive Oxygen Species / metabolism*
  • Response Elements
  • Signal Transduction
  • Tissue Culture Techniques
  • Transfection

Substances

  • Bacterial Proteins
  • Enzyme Inhibitors
  • Heat-Shock Proteins
  • Luminescent Proteins
  • Phosphoproteins
  • Reactive Oxygen Species
  • enhanced cyan fluorescent protein
  • neutrophil cytosol factor 67K
  • yellow fluorescent protein, Bacteria
  • Green Fluorescent Proteins
  • NADPH Oxidases
  • neutrophil cytosolic factor 1