Journal article
Cardiomyocyte-restricted overexpression of extracellular superoxide dismutase increases nitric oxide bioavailability and reduces infarct size after ischemia/reperfusion
Basic research in cardiology, Vol.107(6), pp.305-305
11/01/2012
DOI: 10.1007/s00395-012-0305-1
PMCID: PMC3505528
PMID: 23099819
Abstract
Increased levels of extracellular superoxide dismutase (ecSOD) induced by preconditioning or gene therapy protect the heart from ischemia/reperfusion injury. To elucidate the mechanism responsible for this action, we studied the effects of increased superoxide scavenging on nitric oxide (NO) bioavailability in a cardiac myocyte-specific ecSOD transgenic (Tg) mouse. Results indicated that ecSOD overexpression increased cardiac myocyte-specific ecSOD activity 27.5-fold. Transgenic ecSOD was localized to the sarcolemma and, notably, the cytoplasm of cardiac myocytes. Ischemia/reperfusion injury was attenuated in ecSOD Tg hearts, in which infarct size was decreased and LV functional recovery was improved. Using the ROS spin trap, DMPO, electron paramagnetic resonance (EPR) spectroscopy demonstrated a significant decrease in ROS in Tg hearts during the first 20 min of reperfusion. This decrease in ROS was accompanied by an increase in NO production determined by EPR using the NO spin trap, Fe-MGD. Attenuated ROS in ecSOD Tg myocytes was also supported by decreased production of peroxynitrite (ONOO
−
). Increased NO bioavailability was confirmed by attenuated guanylate cyclase-dependent (p-VASP) signaling. In conclusion, attenuation of ROS levels by cardiac-specific ecSOD overexpression increases NO bioavailability in response to ischemia/reperfusion and protects against reperfusion injury. These findings are the first to demonstrate increased NO bioavailability with attenuation of ROS by direct measurement of these reactive species (EPR, reactive fluorescent dyes) with cardiac-specific ecSOD expression. This is also the first indication that the predominantly extracellular SOD isoform is capable of cytosolic localization that affects myocardial intracellular signal transduction and function.
Details
- Title: Subtitle
- Cardiomyocyte-restricted overexpression of extracellular superoxide dismutase increases nitric oxide bioavailability and reduces infarct size after ischemia/reperfusion
- Creators
- Detlef Obal - University of LouisvilleShujing Dai - University of LouisvilleRachel Keith - University of LouisvilleNeviana Dimova - University of LouisvilleJustin Kingery - University of LouisvilleYu-Ting Zheng - University of LouisvilleJay Zweier - The Ohio State UniversityMurugesan Velayutham - The Ohio State UniversitySumanth D. Prabhu - University of Alabama at BirminghamQianghong Li - University of LouisvilleDaniel Conklin - University of LouisvilleDan Yang - University of Hong KongAruni Bhatnagar - University of LouisvilleRoberto Bolli - University of LouisvilleGregg Rokosh - University of Louisville
- Resource Type
- Journal article
- Publication Details
- Basic research in cardiology, Vol.107(6), pp.305-305
- Publisher
- Springer-Verlag
- DOI
- 10.1007/s00395-012-0305-1
- PMID
- 23099819
- PMCID
- PMC3505528
- ISSN
- 0300-8428
- eISSN
- 1435-1803
- Language
- English
- Date published
- 11/01/2012
- Academic Unit
- Anesthesia
- Record Identifier
- 9984696572702771
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