(Circulation. 2000;101:33.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Gene Expression of Antioxidative Enzymes in the Human Heart
Increased Expression of Catalase in the End-Stage Failing Heart
From the Department of Cardiology and Angiology, University Freiburg, Freiburg, Germany (S.D., U.B., K.B.) and the Department of Cardiology and Pneumology, Georg-August-University Goettingen, Germany (G.H., J.P.).
Correspondence to Juergen Prestle, PhD, Klinikum der Georg-August-Universitaet Goettingen, Zentrum Innere Med/Abt Kardiologie & Pneumologie, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany. E-mail prestle{at}med.uni-goettingen.de
Background—An increase in oxidative stress is suggested to be intimately involved in the pathogenesis of heart failure. However, gene expression of enzymes that metabolize reactive oxygen metabolites has not been investigated in the human heart.
Methods and Results—Myocardial tissue homogenates of the left ventricular wall from hearts in end-stage failure due to dilated (DCM) or ischemic (ICM) cardiomyopathy (n=12 each), as well as from nonfailing donor hearts (n=12), were analyzed for mRNA levels of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), glutathione peroxidase (GPX), and catalase by Northern blot analyses. Protein levels of MnSOD, CuZnSOD, and catalase were determined by Western blot or ELISA. MnSOD, CuZnSOD, and GPX mRNA levels were similar in all 3 groups. In contrast, catalase mRNA levels were found to be increased by 123±23% in DCM hearts and by 93±10% in ICM hearts (P<0.01 each) compared with control hearts. Likewise, catalase protein levels were found to be increased in failing hearts (DCM by 90±10%, ICM by 90±13%; P<0.05 each) compared with control hearts. In addition, the observed upregulation of catalase mRNA and protein in failing hearts was attended by an increased catalase enzyme activity (DCM by 124±16%, ICM by 117±15%; P<0.01 each), whereas MnSOD, CuZnSOD, and GPX enzyme activity levels were unchanged in failing compared with nonfailing myocardium.
Conclusions—Increased oxidative stress in human end-stage heart failure may result in a specific upregulation of catalase gene expression as a compensatory mechanism, whereas SOD and GPX gene expression remain unaffected.
Key Words: antioxidants • enzymes • free radicals • heart failure • molecular biology
This article has been cited by other articles:
 |
|
 |
|
  N. Ardanaz, X.-P. Yang, M. E. Cifuentes, M. J. Haurani, K. W. Jackson, T.-D. Liao, O. A. Carretero, and P. J. Pagano Lack of Glutathione Peroxidase 1 Accelerates Cardiac-Specific Hypertrophy and Dysfunction in Angiotensin II Hypertension Hypertension, January 1, 2010; 55(1): 116 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-i. Choi, T.-i. Kim, K. S. Kim, B.-Y. Kim, S.-y. Ahn, H.-j. Cho, H. K. Lee, H.-S. Cho, and E. K. Kim Decreased Catalase Expression and Increased Susceptibility to Oxidative Stress in Primary Cultured Corneal Fibroblasts from Patients with Granular Corneal Dystrophy Type II Am. J. Pathol., July 1, 2009; 175(1): 248 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Satoh, C. M. Matter, H. Ogita, K. Takeshita, C.-Y. Wang, G. W. Dorn II, and J. K. Liao Inhibition of Apoptosis-Regulated Signaling Kinase-1 and Prevention of Congestive Heart Failure by Estrogen Circulation, June 26, 2007; 115(25): 3197 - 3204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Srivastava, B. Chandrasekar, Y. Gu, J. Luo, T. Hamid, B. G. Hill, and S. D. Prabhu Downregulation of CuZn-superoxide dismutase contributes to {beta}-adrenergic receptor-mediated oxidative stress in the heart Cardiovasc Res, June 1, 2007; 74(3): 445 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Nojiri, T. Shimizu, M. Funakoshi, O. Yamaguchi, H. Zhou, S. Kawakami, Y. Ohta, M. Sami, T. Tachibana, H. Ishikawa, et al. Oxidative Stress Causes Heart Failure with Impaired Mitochondrial Respiration J. Biol. Chem., November 3, 2006; 281(44): 33789 - 33801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Linke, V. Adams, P. C. Schulze, S. Erbs, S. Gielen, E. Fiehn, S. Mobius-Winkler, A. Schubert, G. Schuler, and R. Hambrecht Antioxidative Effects of Exercise Training in Patients With Chronic Heart Failure: Increase in Radical Scavenger Enzyme Activity in Skeletal Muscle Circulation, April 12, 2005; 111(14): 1763 - 1770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Lazar Role of Angiotensin-Converting Enzyme Inhibitors in the Coronary Artery Bypass Patient Ann. Thorac. Surg., March 1, 2005; 79(3): 1081 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hokamaki, H. Kawano, M. Yoshimura, H. Soejima, S. Miyamoto, I. Kajiwara, S. Kojima, T. Sakamoto, S. Sugiyama, N. Hirai, et al. Urinary biopyrrins levels are elevated in relation to severity of heart failure J. Am. Coll. Cardiol., May 19, 2004; 43(10): 1880 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Heymes, J. K. Bendall, P. Ratajczak, A. C. Cave, J.-L. Samuel, G. Hasenfuss, and A. M. Shah Increased myocardial NADPH oxidase activity in human heart failure J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2164 - 2171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Machida, T. Kubota, N. Kawamura, H. Funakoshi, T. Ide, H. Utsumi, Y. Y. Li, A. M. Feldman, H. Tsutsui, H. Shimokawa, et al. Overexpression of tumor necrosis factor-alpha increases production of hydroxyl radical in murine myocardium Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H449 - H455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mak and G. E. Newton The Oxidative Stress Hypothesis of Congestive Heart Failure : Radical Thoughts Chest, December 1, 2001; 120(6): 2035 - 2046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Negoro, K. Kunisada, Y. Fujio, M. Funamoto, M. I. Darville, D. L. Eizirik, T. Osugi, M. Izumi, Y. Oshima, Y. Nakaoka, et al. Activation of Signal Transducer and Activator of Transcription 3 Protects Cardiomyocytes from Hypoxia/Reoxygenation-Induced Oxidative Stress Through the Upregulation of Manganese Superoxide Dismutase Circulation, August 28, 2001; 104(9): 979 - 981. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tsutsui, T. Ide, S. Hayashidani, N. Suematsu, H. Utsumi, R. Nakamura, K. Egashira, and A. Takeshita Greater susceptibility of failing cardiac myocytes to oxygen free radical-mediated injury Cardiovasc Res, January 1, 2001; 49(1): 103 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Wijns and F. Ribichini CRP: does it stand for C oronary R estenosis P rediction? Eur. Heart J., July 2, 2000; 21(14): 1121 - 1123. [PDF]
|
|