HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cai, L. Articles by Kang, Y. J. Search for Related Content PubMed PubMed Citation Articles by Cai, L. Articles by Kang, Y. J. Social Bookmarking                What's this?

Inhibition of Superoxide Generation and Associated Nitrosative Damage Is Involved in Metallothionein Prevention of Diabetic Cardiomyopathy

¹ Department of Medicine, University of Louisville, School of Medicine, Louisville, Kentucky
² Department of Pharmacology and Toxicology, University of Louisville, School of Medicine, Louisville, Kentucky

The mechanisms of metallothionein prevention of diabetic cardiomyopathy are largely unknown. The present study was performed to test whether inhibition of nitrosative damage is involved in metallothionein prevention of diabetic cardiomyopathy. Cardiac-specific metallothionein-overexpressing transgenic (MT-TG) mice and wild-type littermate controls were treated with streptozotocin (STZ) by a single intraperitoneal injection, and both developed diabetes. However, the development of diabetic cardiomyopathy, revealed by histopathological and ultrastructural examination, serum creatine phosphokinase, and cardiac hemodynamic analysis, was significantly observed only in the wild-type, but not in MT-TG, diabetic mice 2 weeks and 6 months after STZ treatment. Formations of superoxide and 3-nitrotyrosine (3-NT), a marker for peroxynitrite-induced protein damage, were detected only in the heart of wild-type diabetic mice. Furthermore, primary cultures of cardiomyocytes from wild-type and MT-TG mice were exposed to lipopolysaccharide/tumor necrosis factor- for generating intracellular peroxynitrite. Increases in 3-NT formation and cytotoxicity were observed in wild-type, but not in MT-TG, cardiomyocytes. Either urate, a peroxynitrite-specific scavenger, or Mn(111) tetrakis 1-methyl 4-pyridyl porphyrin pentachloride (MnTMPyP), a superoxide dismutase mimic, significantly inhibited the formation of 3-NT along with a significant prevention of cytotoxicity. These results thus suggest that metallothionein prevention of diabetic cardiomyopathy is mediated, at least in part, by suppression of superoxide generation and associated nitrosative damage.

Abbreviations: 3-NT, 3-nitrotyrosine; CPK, creatine phosphokinase; LDH, lactate dehydrogenase; LPS, lipopolysaccharide; LVEDP, left ventricular end-diastolic pressure; LVMDP, left ventricular minimum diastolic pressure; MnTMPyP, Mn(111) tetrakis 1-methyl 4-pyridyl porphyrin pentachloride; MT-TG, metallothionein-overexpressing transgenic; OD, optical density; RNS, reactive nitrogen species; ROS, reactive oxygen species; SIN-1, 3-morpholinosydnonimine; SOD, superoxide dismutase; STZ, streptozotocin; TNF-, tumor necrosis factor-

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H.-J. Maeng, M.-H. Kim, H.-E. Jin, S. M. Shin, T. Tsuruo, S. G. Kim, D.-D. Kim, C.-K. Shim, and S.-J. Chung Functional Induction of P-glycoprotein in the Blood-Brain Barrier of Streptozotocin-Induced Diabetic Rats: Evidence for the Involvement of Nuclear Factor-{kappa}B, a Nitrosative Stress-Sensitive Transcription Factor, in the Regulation Drug Metab. Dispos., November 1, 2007; 35(11): 1996 - 2005. [Abstract] [Full Text] [PDF]

				X. SHEN and K. E. BORNFELDT Mouse Models for Studies of Cardiovascular Complications of Type 1 Diabetes Ann. N.Y. Acad. Sci., April 1, 2007; 1103(1): 202 - 217. [Abstract] [Full Text] [PDF]

				L. Cai, Y. Wang, G. Zhou, T. Chen, Y. Song, X. Li, and Y. J. Kang Attenuation by Metallothionein of Early Cardiac Cell Death via Suppression of Mitochondrial Oxidative Stress Results in a Prevention of Diabetic Cardiomyopathy J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1688 - 1697. [Abstract] [Full Text] [PDF]

				Y. J. Kang Metallothionein redox cycle and function. Experimental Biology and Medicine, October 1, 2006; 231(9): 1459 - 1467. [Abstract] [Full Text] [PDF]

				C. X. Fang, S. Wu, and J. Ren Intracerebral Hemorrhage Elicits Aberration in Cardiomyocyte Contractile Function and Intracellular Ca2+ Transients Stroke, July 1, 2006; 37(7): 1875 - 1882. [Abstract] [Full Text] [PDF]

				X. Yang, T. A. Doser, C. X. Fang, J. M. Nunn, R. Janardhanan, M. Zhu, N. Sreejayan, M. T. Quinn, and J. Ren Metallothionein prolongs survival and antagonizes senescence-associated cardiomyocyte diastolic dysfunction: role of oxidative stress FASEB J, May 1, 2006; 20(7): 1024 - 1026. [Abstract] [Full Text] [PDF]

				M. Ayaz and B. Turan Selenium prevents diabetes-induced alterations in [Zn2+]i and metallothionein level of rat heart via restoration of cell redox cycle Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1071 - H1080. [Abstract] [Full Text] [PDF]

				J. Wang, Y. Song, L. Elsherif, Z. Song, G. Zhou, S. D. Prabhu, J. T. Saari, and L. Cai Cardiac Metallothionein Induction Plays the Major Role in the Prevention of Diabetic Cardiomyopathy by Zinc Supplementation Circulation, January 31, 2006; 113(4): 544 - 554. [Abstract] [Full Text] [PDF]