title: Overexpression of tumor necrosis factor-alpha increases production of hydroxyl radical in murine myocardium.
abstract: Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor-alpha develop congestive heart failure with myocardial inflammation. The purpose of this study was to investigate the effects of tumor necrosis factor-alpha on reactive oxygen species (ROS) in this mouse model of cardiomyopathy. Myocardial production of hydroxyl radical detected by electron spin resonance spectroscopy was significantly increased in TG. Myocardial expression of Mn-SOD was significantly decreased in TG, whereas that of Cu,Zn-SOD was unaltered. Myocardial expression of catalase was unchanged, whereas that of glutathione peroxidase was significantly increased, in TG. Histological analysis revealed that macrophages and CD4-positive lymphocytes were increased in TG myocardium. To investigate whether these infiltrating inflammatory cells were the source of ROS, we treated TG mice with cyclophosphamide for 7 days. Although cyclophosphamide significantly suppressed the infiltration of inflammatory cells, it did not diminish the production of hydroxyl radical in TG myocardium. Damaged myocytes, but not infiltrating inflammatory cells, may be the source of ROS in TG.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Machida
authors.forename: Toru
authors.initials: T
authors.lastname: Kubota
authors.forename: Natsumi
authors.initials: N
authors.lastname: Kawamura
authors.forename: Hajime
authors.initials: H
authors.lastname: Funakoshi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ide
authors.forename: Hideo
authors.initials: H
authors.lastname: Utsumi
authors.forename: Yun You
authors.initials: YY
authors.lastname: Li
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Feldman
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D017665:Hydroxyl Radical; D003520:Cyclophosphamide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase