Overexpression of wild-type human SOD1 in mice prevents myocardial reperfusion injury

P. Wang, Philip Chun Wong, S. Sankarapandi, H. Qin, V. P. Chacko, J. L. Zweier

Research output: Contribution to journalArticle

Abstract

While superoxide derived free radicals are generated in ihe postischemic heart and are important mediator of reperfusion injury, there is controversy regarding whether genetic engineering increased expression ol the superoxide metabolizing enzyme copper zine superoxide dismutase (SOD1) can prevent cellular anjury. Therefore, studies were performed in isolated hearts from transgenic mice expressing increased levels of wild-type human SOD1 (TG) or in nontransgenic controls (NT) with normal SOD levels (N=16/grp). Measurements of contractile function, oxygen free radicals (OFR), and high energy phosphates (HFP) were performed in hearts before and after 30 min of 37°C ischemia (1) followed In 45 min reperfusion (R). OFR generation and HEP were measured using electronic paramagnetic resonance (EPR) spin trapping (using 40mM DMPO) and 31P nuclear magnetic resonance (NMR). respectively. Contractile function and infarction were studied in parallel. NT hearts exhibited a typical burst generation of OFR in the first 2 min of reflow, with more than 10 fold rise above preischemic levels, while no OFR was seen in TG hearts which had 6-8 fold increased expression of SOD1 (measured by Western Blot). After 45 min of R, TG hearts exhibited much higher recovery of contractile function with 21.9±.04% vs 10.9 ±0.3% recovery of rate pressure product (p≤0.05). This correlated with higher recovery of ATP (61.8±7.4% vs 29.6±3.1%, p≤0.()5) and phosphocreatine (70.9±8.9% vs 51.7±4.2%, p≤0 05). Myocardial infarction after 45 min reflow was measured by TTC staining. In TG hearts much less infarction was seen than in NT hearts. 14.2±1.1% vs 30.77±2.8%, p≤0.01. Thus, genetic engineering of increased intrazellular SOD expression prevents postischemic free radical generation and confers resistance to myocardial reperfusion injury.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997

Fingerprint

Myocardial Reperfusion Injury
heart
Free Radicals
mice
Reactive Oxygen Species
Oxygen
oxygen
Genetic engineering
Genetic Engineering
infarction
genetic engineering
Recovery
Superoxides
superoxide anion
Infarction
superoxide dismutase
phosphocreatine
Spin Trapping
Phosphocreatine
myocardial infarction

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Wang, P., Wong, P. C., Sankarapandi, S., Qin, H., Chacko, V. P., & Zweier, J. L. (1997). Overexpression of wild-type human SOD1 in mice prevents myocardial reperfusion injury. FASEB Journal, 11(3).

Overexpression of wild-type human SOD1 in mice prevents myocardial reperfusion injury. / Wang, P.; Wong, Philip Chun; Sankarapandi, S.; Qin, H.; Chacko, V. P.; Zweier, J. L.

In: FASEB Journal, Vol. 11, No. 3, 1997.

Research output: Contribution to journalArticle

Wang, P, Wong, PC, Sankarapandi, S, Qin, H, Chacko, VP & Zweier, JL 1997, 'Overexpression of wild-type human SOD1 in mice prevents myocardial reperfusion injury', FASEB Journal, vol. 11, no. 3.
Wang, P. ; Wong, Philip Chun ; Sankarapandi, S. ; Qin, H. ; Chacko, V. P. ; Zweier, J. L. / Overexpression of wild-type human SOD1 in mice prevents myocardial reperfusion injury. In: FASEB Journal. 1997 ; Vol. 11, No. 3.
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abstract = "While superoxide derived free radicals are generated in ihe postischemic heart and are important mediator of reperfusion injury, there is controversy regarding whether genetic engineering increased expression ol the superoxide metabolizing enzyme copper zine superoxide dismutase (SOD1) can prevent cellular anjury. Therefore, studies were performed in isolated hearts from transgenic mice expressing increased levels of wild-type human SOD1 (TG) or in nontransgenic controls (NT) with normal SOD levels (N=16/grp). Measurements of contractile function, oxygen free radicals (OFR), and high energy phosphates (HFP) were performed in hearts before and after 30 min of 37°C ischemia (1) followed In 45 min reperfusion (R). OFR generation and HEP were measured using electronic paramagnetic resonance (EPR) spin trapping (using 40mM DMPO) and 31P nuclear magnetic resonance (NMR). respectively. Contractile function and infarction were studied in parallel. NT hearts exhibited a typical burst generation of OFR in the first 2 min of reflow, with more than 10 fold rise above preischemic levels, while no OFR was seen in TG hearts which had 6-8 fold increased expression of SOD1 (measured by Western Blot). After 45 min of R, TG hearts exhibited much higher recovery of contractile function with 21.9±.04{\%} vs 10.9 ±0.3{\%} recovery of rate pressure product (p≤0.05). This correlated with higher recovery of ATP (61.8±7.4{\%} vs 29.6±3.1{\%}, p≤0.()5) and phosphocreatine (70.9±8.9{\%} vs 51.7±4.2{\%}, p≤0 05). Myocardial infarction after 45 min reflow was measured by TTC staining. In TG hearts much less infarction was seen than in NT hearts. 14.2±1.1{\%} vs 30.77±2.8{\%}, p≤0.01. Thus, genetic engineering of increased intrazellular SOD expression prevents postischemic free radical generation and confers resistance to myocardial reperfusion injury.",
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AB - While superoxide derived free radicals are generated in ihe postischemic heart and are important mediator of reperfusion injury, there is controversy regarding whether genetic engineering increased expression ol the superoxide metabolizing enzyme copper zine superoxide dismutase (SOD1) can prevent cellular anjury. Therefore, studies were performed in isolated hearts from transgenic mice expressing increased levels of wild-type human SOD1 (TG) or in nontransgenic controls (NT) with normal SOD levels (N=16/grp). Measurements of contractile function, oxygen free radicals (OFR), and high energy phosphates (HFP) were performed in hearts before and after 30 min of 37°C ischemia (1) followed In 45 min reperfusion (R). OFR generation and HEP were measured using electronic paramagnetic resonance (EPR) spin trapping (using 40mM DMPO) and 31P nuclear magnetic resonance (NMR). respectively. Contractile function and infarction were studied in parallel. NT hearts exhibited a typical burst generation of OFR in the first 2 min of reflow, with more than 10 fold rise above preischemic levels, while no OFR was seen in TG hearts which had 6-8 fold increased expression of SOD1 (measured by Western Blot). After 45 min of R, TG hearts exhibited much higher recovery of contractile function with 21.9±.04% vs 10.9 ±0.3% recovery of rate pressure product (p≤0.05). This correlated with higher recovery of ATP (61.8±7.4% vs 29.6±3.1%, p≤0.()5) and phosphocreatine (70.9±8.9% vs 51.7±4.2%, p≤0 05). Myocardial infarction after 45 min reflow was measured by TTC staining. In TG hearts much less infarction was seen than in NT hearts. 14.2±1.1% vs 30.77±2.8%, p≤0.01. Thus, genetic engineering of increased intrazellular SOD expression prevents postischemic free radical generation and confers resistance to myocardial reperfusion injury.

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