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Loss of endogenous H 2 O 2 ‐induced inhibition of ASIC1‐mediated Ca 2+ influx in pulmonary artery smooth muscle cells following chronic hypoxia
Author(s) -
Plomaritas Danielle R,
Herbert Lindsay M,
Resta Thomas C,
Walker Benjimen R,
Jernigan Nikki L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1140.4
Subject(s) - hypoxic pulmonary vasoconstriction , hypoxia (environmental) , pulmonary hypertension , chemistry , endogeny , superoxide dismutase , medicine , endocrinology , downregulation and upregulation , catalase , vasoconstriction , acid sensing ion channel , superoxide , oxidative stress , biochemistry , ion channel , oxygen , receptor , enzyme , organic chemistry , gene
Our laboratory has demonstrated an important role for acid‐sensing ion channel 1 (ASIC1) in mediating increased pulmonary arterial smooth muscle cell (PASMC) Ca 2+ influx and enhanced agonist‐induced vasoconstriction following chronic hypoxia (CH)‐induced pulmonary hypertension. ASIC1 activity is highly sensitive to changes in the redox state of the cell; in particular, hydrogen peroxide (H 2 O 2 ) has been shown to inhibit ASIC1 function. Furthermore, alterations in reactive oxygen species are known to contribute to the pathogenesis of pulmonary hypertension. Therefore, we hypothesize the increased ASIC1‐mediated store‐operated calcium entry (SOCE) in PASMCs following CH is due to decreased H 2 O 2 , attributable to a down regulation of superoxide dismutase (SOD). We found that PEG‐catalase augmented ASIC1‐dependent SOCE in PASMCs from control rats, but was without effect on SOCE in PASMCs from CH rats (4 wks @ 380 Torr). However, the addition of H 2 O 2 inhibited SOCE in both groups. Additionally, SOD1 and SOD3 protein expression were decreased in isolated pulmonary arteries from CH rats compared to control. Together these data suggest that downregulation of SOD1 and SOD3 following CH results in a loss of endogenous H 2 O 2 ‐induced inhibition of ASIC1‐dependent SOCE in PASMC. This work is supported by NIH HL‐09258 (NLJ) and HL‐07736 (BRW).