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Thioredoxin‐1 is necessary for hypoxia‐induced cell proliferation in human pulmonary artery smooth muscle cells
Author(s) -
Jin Yi,
Tipple Trent E,
Chicoine Louis G,
Nelin Leif D,
Chen Bernadette
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.1141.9
Subject(s) - hypoxia (environmental) , protein kinase b , ly294002 , pi3k/akt/mtor pathway , cell growth , microbiology and biotechnology , phosphorylation , thioredoxin , transfection , cancer research , pharmacology , cell , small interfering rna , biology , chemistry , signal transduction , cell culture , endocrinology , biochemistry , oxidative stress , organic chemistry , genetics , oxygen
To test the hypothesis that hypoxia increases Trx‐1 in human pulmonary artery smooth muscle cells (hPASMC), resulting in an increase in cell proliferation, hPASMC were exposed to normoxia (21% O2) or hypoxia (1% O2) and Trx‐1 activity or expression were manipulated using an siRNA against Trx‐1 or the putative pharmacological inhibitor PX‐12. Trx‐1 protein expression was 2‐fold greater in the hypoxic hPASMC than in normoxic hPASMC at 48 h. Hypoxic exposure also resulted in significantly greater viable cell numbers after 120 h than in normoxic hPASMC. Trx‐1 expression was suppressed by Trx‐1 siRNA transfection and the hypoxia‐induced increase in cell proliferation was prevented by Trx‐1 siRNA. The pharmacological Trx‐1 inhibitor PX‐12 also inhibited the hypoxia‐induced increase in hPASMC proliferation. The hypoxia‐induced increase in HRE‐luciferase activity was prevented by treatment with either the Trx‐1 siRNA or PX‐12. Akt was phosphorylated at 2h and 24h in the hypoxic hPASMC, and Akt phosphorylation was prevented by treatment with the Trx‐1 siRNA. Inhibition of the PI3K‐Akt pathway using LY294002 resulted in a decrease in proliferation in hPASMC. Our data demonstrates that hypoxia results in Trx‐1‐mediated cell proliferation in hPASMCs, at least partly through activation of HIF signaling and the PI3K‐Akt pathway. Trx‐1 may be a potential therapeutic target for pulmonary hypertension.