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Alterations of Orai, STIM, and TRPC Expression and Store‐ Operated Calcium Entry in Pulmonary Arteries of Monocrotaline‐Induced Pulmonary Hypertensive Rats
Author(s) -
Lin Mo-Jun,
Liu Qing,
Liu Xiao-Ru,
Wang Rui-Xing,
Liu Cheng,
Sham James S.K.
Publication year - 2012
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.26.1_supplement.873.18
Subject(s) - trpc , orai1 , trpc1 , stim1 , trpc6 , transient receptor potential channel , chemistry , western blot , medicine , endocrinology , microbiology and biotechnology , pharmacology , receptor , calcium , biology , biochemistry , gene
Pulmonary hypertension (PH) is associated with alterations in Ca 2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Previous studies show that store‐operated Ca 2+ entry (SOCE) is enhanced in PASMCs of chronic hypoxia‐ and monocrotaline (MCT)‐induced PH rats, and idiopathic PH patients. Since the SOCE pathway is composed of many different proteins and channels, including the sarcoplasmic Ca 2+ sensor stromal interaction molecules (STIM), Orai channels, and transient receptor potential channels, we sought to examine the alterations in the expression of these molecular constituents of SOCE in the PASM of MCT‐induced PH rats. Rats developed severe PH and right ventricular hypertrophy within three weeks after a single injection of MCT. Quantitative RT‐PCR found that there was significant increase in the expression of STIM2, Orai1, Orai2, TRPC1, and TRPC4, whereas the expression of STIM1, Orai3, and TRPC6 was unchanged. Unregulation of Orai1, TRPC1, and TRPC4 proteins were also verified by Western blot. Moreover, the time‐course of increase in the expression of STIM2, Orai1, and TRPC1 were similar to that of the increase in SOCE induced PA contraction. These results suggest that multiple components of the SOCE pathways are altered during PH and contribute synergistically to the enhanced SOCE in PASMCs. (This work is supported by NSFC 30670772 and 31171104, FJMU09ZD010, NSF‐Fujian 2010J01173, and R01‐HL075134)