Overexpression of tumor necrosis factor-alpha increases production of hydroxyl radical in murine myocardium.
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.
Machida
Yoji
Y
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Kubota
Toru
T
Kawamura
Natsumi
N
Funakoshi
Hajime
H
Ide
Tomomi
T
Utsumi
Hideo
H
Li
Yun You
YY
Feldman
Arthur M
AM
Tsutsui
Hiroyuki
H
Shimokawa
Hiroaki
H
Takeshita
Akira
A
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*
D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D017665:Hydroxyl Radical; D003520:Cyclophosphamide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase