Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: implications for diseases in the cardiovascular system

Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: implications for diseases in... Reactive oxygen species (ROS) and the cellular thiol redox state are crucial mediators of multiple cell processes like growth, differentiation, and apoptosis. Excessive ROS production or oxidative stress is associated with several diseases, including cardiovascular disorders like ischemia-reperfusion. To prevent ROS-induced disorders, the heart is equipped with effective antioxidant systems. Key players in defense against oxidative stress are members of the thioredoxin-fold family of proteins. Of these, thioredoxins and glutaredoxins maintain a reduced intracellular redox state in mammalian cells by the reduction of protein thiols. The reversible oxidation of Cys-Gly-Pro-Cys or Cys-Pro(Ser)-Tyr-Cys active site cysteine residues is used in reversible electron transport. Thioredoxins and glutaredoxins belong to corresponding systems consisting of NADPH, thioredoxin reductase, and thioredoxin or NADPH, glutathione reductase, glutathione, and glutaredoxin, respectively. Thioredoxin as well as glutaredoxin activities appear to be very important for the progression and severity of several cardiovascular disorders. These proteins function not only as antioxidants, they inhibit or activate apoptotic signaling molecules like apoptosis signal-regulating kinase 1 and Ras or transcription factors like NF-κB. Thioredoxin activity is regulated by the endogenous inhibitor thioredoxin-binding protein 2 (TBP-2), indicating an important role of the balance between thioredoxin and TBP-2 levels in cardiovascular diseases. In this review, we will summarize cardioprotective effects of endogenous thioredoxin and glutaredoxin systems as well as the high potential in clinical applications of exogenously applied thioredoxin or glutaredoxin or the induction of endogenous thioredoxin and glutaredoxin systems. oxidative stress; thiol-disulfide oxidoreductases; apoptotic signaling; myocardial remodeling; glutathione Address for reprint requests and other correspondence: A. Holmgren, The Medical Nobel Inst. for Biochemistry, Dept. of Medical Biochemistry and Biophysics, Karolinska Inst., SE-17177 Stockholm, Sweden (e-mail: arne.holmgren@ki.se ) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Heart and Circulatory Physiology The American Physiological Society

Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: implications for diseases in the cardiovascular system

Loading next page...
 
/lp/the-american-physiological-society/thiol-based-mechanisms-of-the-thioredoxin-and-glutaredoxin-systems-FdwHSNcE3z

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6135
eISSN
1522-1539
DOI
10.1152/ajpheart.01162.2006
pmid
17172268
Publisher site
See Article on Publisher Site

Abstract

Reactive oxygen species (ROS) and the cellular thiol redox state are crucial mediators of multiple cell processes like growth, differentiation, and apoptosis. Excessive ROS production or oxidative stress is associated with several diseases, including cardiovascular disorders like ischemia-reperfusion. To prevent ROS-induced disorders, the heart is equipped with effective antioxidant systems. Key players in defense against oxidative stress are members of the thioredoxin-fold family of proteins. Of these, thioredoxins and glutaredoxins maintain a reduced intracellular redox state in mammalian cells by the reduction of protein thiols. The reversible oxidation of Cys-Gly-Pro-Cys or Cys-Pro(Ser)-Tyr-Cys active site cysteine residues is used in reversible electron transport. Thioredoxins and glutaredoxins belong to corresponding systems consisting of NADPH, thioredoxin reductase, and thioredoxin or NADPH, glutathione reductase, glutathione, and glutaredoxin, respectively. Thioredoxin as well as glutaredoxin activities appear to be very important for the progression and severity of several cardiovascular disorders. These proteins function not only as antioxidants, they inhibit or activate apoptotic signaling molecules like apoptosis signal-regulating kinase 1 and Ras or transcription factors like NF-κB. Thioredoxin activity is regulated by the endogenous inhibitor thioredoxin-binding protein 2 (TBP-2), indicating an important role of the balance between thioredoxin and TBP-2 levels in cardiovascular diseases. In this review, we will summarize cardioprotective effects of endogenous thioredoxin and glutaredoxin systems as well as the high potential in clinical applications of exogenously applied thioredoxin or glutaredoxin or the induction of endogenous thioredoxin and glutaredoxin systems. oxidative stress; thiol-disulfide oxidoreductases; apoptotic signaling; myocardial remodeling; glutathione Address for reprint requests and other correspondence: A. Holmgren, The Medical Nobel Inst. for Biochemistry, Dept. of Medical Biochemistry and Biophysics, Karolinska Inst., SE-17177 Stockholm, Sweden (e-mail: arne.holmgren@ki.se )

Journal

AJP - Heart and Circulatory PhysiologyThe American Physiological Society

Published: Mar 1, 2007

There are no references for this article.