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Tumor necrosis factor‐alpha induces gp91phox, Nox1, Nox4 and eNos in rat myocardium and cardiomyocyte cell line
Author(s) -
Haque Masudul,
Sember Courtney,
Guggilam Anuradha,
Hartfield Julie N,
Sehgal Inder,
Lucchesi Pamela A,
Francis Joseph
Publication year - 2006
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.20.5.lb8-d
Subject(s) - tumor necrosis factor alpha , enos , nox4 , nox1 , in vivo , pentoxifylline , medicine , oxidative stress , endocrinology , cytokine , in vitro , biology , nitric oxide , nitric oxide synthase , nadph oxidase , biochemistry , microbiology and biotechnology
Tumor necrosis factor‐alpha (TNF‐α) is a multifunctional cytokine that induces myocardial dysfunction, thereby contributing to the pathogenesis of cardiovascular disease. Pentoxifylline (PTX) is a xanthine derivative known to inhibit the production of TNF‐α. In this study, we determined the in vivo and in vitro effects of TNF‐α on oxidative stress in the left ventricle (LV) and in rat cardiomyocyte cultures. Methods In vivo : Rats were treated with TNF‐α @ 30 μg/kg BW/day or saline for 5 days. One group of rats received TNF‐α and PTX @ 20 mg/kg BW. LV function was measured at baseline and on day 5 using echocardiography. Subsequently, rats were sacrificed and the gene expression for gp91phox, Nox1, Nox4, and eNOS in the myocardium was measured using real‐time PCR. In vitro : H9C2 rat cardiomyocyte cultures were treated with 5 ng/ml of TNF‐α alone or 30 min pretreatment with PTX and TNF‐α for 6h and the cells were harvested for gene expression studies. Results TNF‐α treatment induced a significant increase in gp91phox, Nox1, Nox4 and eNOS in rat myocardium and in cardiomyocyte cultures. Pretreatment with PTX prevented TNF‐α induced gene expression. Conclusions Both in vitro and in vivo treatment with TNF‐α increases gene expression for eNOS, gp91phox, Nox1, and Nox4 in cardiomyocyte cultures and LV tissues. TNF‐α modulate oxidative stress in vitro cardiomyocyte cultures and in the rat myocardium.