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Chronic Hypoxia increases Orai1 and Orai2 Expression in Pulmonary Arterial Smooth Muscle
Author(s) -
Lu Wenju,
Undem Clark,
Wang Jian,
Sylvester J T,
Shimoda Larissa A
Publication year - 2011
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.25.1_supplement.1034.6
Subject(s) - hypoxia (environmental) , cardiology , medicine , chemistry , oxygen , organic chemistry
Chronic hypoxia (CH) causes pulmonary arterial smooth muscle cell (PASMC) contraction and proliferation. We have shown that resting intracellular calcium concentration ([Ca 2+ ] i ) was elevated in PASMCs from chronically hypoxic rats (10%O 2 ; 21 days) due to enhanced Ca 2+ influx through store‐operated Ca 2+ channels, which are likely composed of TRPC and Orai proteins and interact with Stim proteins. In this study, we investigated the effects of hypoxia on the expression of Orai1, 2, 3 and Stim1 and 2. We found that CH increased Orai1 and Orai2 and decreased Stim2 mRNA and protein levels in distal pulmonary arteries from rats; however, the mRNA and protein expression of Orai3 and Stim1 were not altered. Ex vivo exposure to prolonged hypoxia (4% O 2 , 60 h) increased mRNA and protein expression of Orai1 and Orai2 in rat PASMCs; however, it did not alter either mRNA or protein expression of Orai3, Stim1 or Stim2. Overexpressing hypoxia inducible factor‐1 (HIF‐1) increased Orai2 mRNA and protein expression, without changing Orail expression in PASMCs, and the hypoxia‐induced increase in Orai2 mRNA and protein expression were diminished in pulmonary arteries from HIF‐1α herozygous null mice. Thus, we conclude that CH increases Orai1 and Orai2 expression in PASMCs, and that the latter is HIF‐1α‐dependent. The change in Orai1 and Orai2 expression may contribute to the enhanced resting [Ca 2+ ] i in chronically hypoxic PASMCs.