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Superoxide enhances cell proliferation in pulmonary artery adventitial fibroblasts from chronically hypoxic calves and augments expression of the redox‐sensitive transcription factor, Egr‐1
Author(s) -
Martinez Maylyn,
Hartney Tanya,
Frid Maria,
Stenmark Kurt,
NozikGrayck Eva
Publication year - 2010
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.24.1_supplement.701.6
Subject(s) - xanthine oxidase , superoxide dismutase , microbiology and biotechnology , reactive oxygen species , superoxide , xanthine , cell growth , transcription factor , hypoxia (environmental) , in vivo , andrology , biology , chemistry , endocrinology , medicine , biochemistry , oxidative stress , enzyme , oxygen , gene , organic chemistry
Superoxide (O 2 − ) has been implicated in chronic hypoxia‐induced pulmonary hypertension (CHPH) and pulmonary vascular remodeling. In a calf model of CHPH, the pulmonary artery adventitial fibroblast (PAAF) proliferates in vivo and in vitro and contributes to vascular remodeling. Hypoxia‐induced proliferation of PAAF is mediated in part by a redox‐sensitive transcription factor, early growth response‐1 (Egr‐1). We hypothesized that ROS are responsible for the proliferation observed in PAAF from the chronically hypoxic (HA) calf through Egr‐1. We cultured PAAF isolated from HA neonatal calves in the presence or absence of the antioxidant, superoxide dismutase (SOD, 200 U/ml) for up to 6 days and measured changes in cell counts by hemocytometer and MTT assay. We exposed cells to xanthine and xanthine oxidase (8 mU/mL) to generate O 2 − , and measured Egr‐1 mRNA expression by real‐time PCR. We found that SOD decreased proliferation in PAAF from HA calves. Treatment of HA PAAF with xanthine/xanthine oxidase increased Egr‐1 mRNA expression by 2 fold (p<0.05 by unpaired t‐test). These data provide evidence that O 2 − contributes to the proliferation of PAAF from HA calves and support the hypothesis that O 2 − may regulate cell proliferation by upregulating the transcription factor, Egr‐1.