Document Detail

Chronic hypoxia limits H2O2-induced inhibition of ASIC1-dependent store-operated calcium entry in pulmonary arterial smooth muscle.
MedLine Citation:
PMID:  24993130     Owner:  NLM     Status:  Publisher    
Our laboratory shows that acid-sensing ion channel 1 (ASIC1) contributes to the development of hypoxic pulmonary hypertension by augmenting store-operated Ca(2+) entry (SOCE) that is associated with enhanced agonist-induced vasoconstriction and arterial remodeling. However, this enhanced Ca(2+) influx following chronic hypoxia (CH) is not dependent on an increase ASIC1 protein expression in pulmonary arterial smooth muscle cells (PASMC). It is well documented that hypoxic pulmonary hypertension is associated with changes in redox potential and reactive oxygen species homeostasis. ASIC1 is a redox-sensitive channel showing increase activity in response to reducing agents; representing an alternative mechanism of regulation. We hypothesize that the enhanced SOCE following CH results from removal of an inhibitory effect of hydrogen peroxide (H2O2) on ASIC1. We found that CH increased PASMC superoxide (O2 (•-)) and decreased rat pulmonary arterial H2O2 levels. This decrease in H2O2 is a result of decreased Cu/Zn superoxide dismutase expression and activity as well as increased glutathione peroxidase (GPx) expression and activity following CH. Whereas H2O2 inhibited ASIC1-dependent SOCE in PASMC from control and CH animals, addition of catalase augmented ASIC1-mediated SOCE in PASMC from control rats but had no further effect in PASMC from CH rats. These data suggest that under control conditions H2O2 inhibits ASIC1-dependent SOCE. Furthermore, H2O2 levels are decreased following CH as a result of diminished dismutation of O2 (•-) and increased H2O2 catalysis through GPx, leading to augmented ASIC1-dependent SOCE.
Danielle R Plomaritas; Lindsay M Herbert; Tracylyn R Yellowhair; Thomas C Resta; Laura V Gonzalez Bosc; Benjimen R Walker; Nikki L Jernigan
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-3
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  -     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Journal of Physiology - Lung Cellular and Molecular Physiology.
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