Overexpression of tumor necrosis factor-α increases production of hydroxyl radical in murine myocardium

Yoji Machida, Toru Kubota, Natsumi Kawamura, Hajime Funakoshi, Tomomi Ide, Hideo Utsumi, Yun You Li, Arthur M. Feldman, Hiroyuki Tsutsui, Hiroaki Shimokawa, Akira Takeshita

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor-α develop congestive heart failure with myocardial inflammation. The purpose of this study was to investigate the effects of tumor necrosis factor-α 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number2 53-2
Publication statusPublished - Feb 1 2003

Fingerprint

Hydroxyl Radical
Reactive Oxygen Species
Myocardium
Tumor Necrosis Factor-alpha
Cyclophosphamide
Transgenic Mice
CD4-Positive T-Lymphocytes
Electron Spin Resonance Spectroscopy
Glutathione Peroxidase
Cardiomyopathies
Catalase
Muscle Cells
Superoxide Dismutase
Heart Failure
Macrophages
Inflammation

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Overexpression of tumor necrosis factor-α increases production of hydroxyl radical in murine myocardium. / Machida, Yoji; Kubota, Toru; Kawamura, Natsumi; Funakoshi, Hajime; Ide, Tomomi; Utsumi, Hideo; Li, Yun You; Feldman, Arthur M.; Tsutsui, Hiroyuki; Shimokawa, Hiroaki; Takeshita, Akira.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 284, No. 2 53-2, 01.02.2003.

Research output: Contribution to journalArticle

Machida, Y, Kubota, T, Kawamura, N, Funakoshi, H, Ide, T, Utsumi, H, Li, YY, Feldman, AM, Tsutsui, H, Shimokawa, H & Takeshita, A 2003, 'Overexpression of tumor necrosis factor-α increases production of hydroxyl radical in murine myocardium', American Journal of Physiology - Heart and Circulatory Physiology, vol. 284, no. 2 53-2.
Machida, Yoji ; Kubota, Toru ; Kawamura, Natsumi ; Funakoshi, Hajime ; Ide, Tomomi ; Utsumi, Hideo ; Li, Yun You ; Feldman, Arthur M. ; Tsutsui, Hiroyuki ; Shimokawa, Hiroaki ; Takeshita, Akira. / Overexpression of tumor necrosis factor-α increases production of hydroxyl radical in murine myocardium. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 284, No. 2 53-2.
@article{5700749ba54d456f94aaa54edaa16b85,
title = "Overexpression of tumor necrosis factor-α increases production of hydroxyl radical in murine myocardium",
abstract = "Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor-α develop congestive heart failure with myocardial inflammation. The purpose of this study was to investigate the effects of tumor necrosis factor-α 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.",
author = "Yoji Machida and Toru Kubota and Natsumi Kawamura and Hajime Funakoshi and Tomomi Ide and Hideo Utsumi and Li, {Yun You} and Feldman, {Arthur M.} and Hiroyuki Tsutsui and Hiroaki Shimokawa and Akira Takeshita",
year = "2003",
month = "2",
day = "1",
language = "English",
volume = "284",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "2 53-2",

}

TY - JOUR

T1 - Overexpression of tumor necrosis factor-α increases production of hydroxyl radical in murine myocardium

AU - Machida, Yoji

AU - Kubota, Toru

AU - Kawamura, Natsumi

AU - Funakoshi, Hajime

AU - Ide, Tomomi

AU - Utsumi, Hideo

AU - Li, Yun You

AU - Feldman, Arthur M.

AU - Tsutsui, Hiroyuki

AU - Shimokawa, Hiroaki

AU - Takeshita, Akira

PY - 2003/2/1

Y1 - 2003/2/1

N2 - Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor-α develop congestive heart failure with myocardial inflammation. The purpose of this study was to investigate the effects of tumor necrosis factor-α 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.

AB - Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor-α develop congestive heart failure with myocardial inflammation. The purpose of this study was to investigate the effects of tumor necrosis factor-α 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.

UR - http://www.scopus.com/inward/record.url?scp=0037307184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037307184&partnerID=8YFLogxK

M3 - Article

C2 - 12388222

AN - SCOPUS:0037307184

VL - 284

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 2 53-2

ER -