Ecto-5'-nucleotidase plays a role in the cardioprotective effects of heat shock protein 72 in ischemia-reperfusion injury in rat hearts.

Abstract

OBJECTIVE:

Heat shock protein 72 (HSP72) is involved in the myocardial self-preservation system under several conditions such as ischemia-reperfusion injury or late preconditioning. However, its mechanism is not fully understood. Ecto-5'-nucleotidase is a key enzyme for synthesizing adenosine and plays an important role in ischemic preconditioning. In this study, we tested the hypothesis that ecto-5'-nucleotidase plays a role in the cardioprotection of HSP72.

METHODS:

Rat hearts (H group, n=6) were transfected with HSP72 gene by an intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome complex. Control hearts (C group, n=6) were transfected with the beta-galactosidase gene. Following 30 min of normothermic ischemia, grafts were reperfused using Langendorff apparatus.

RESULTS:

The activity of ecto-5'-nucleotidase was significantly higher in H group than C group both before and after ischemia-reperfusion (H vs. C; 0.51+/-0.05 vs. 0.29+/-0.06, and 1.41+/-0.15 vs. 0.85+/-0.11 nmol/mg protein/min, P<0.05). H group also showed significant better functional recoveries than C group (P<0.05), as well as less creatine phosphokinase leakage (4.4+/-2.8 vs. 14.2+/-3.4 mU/min, P<0.05) and higher adenosine release (247.5+/-35.1 vs. 54.3+/-1.7 pmol/min, P<0.05). Administration of alpha,beta-methylene adenosine diphosphate (AMP-CP), an inhibitor of ecto-5'-nucleotidase, significantly diminished the tolerance to ischemia-reperfusion injury in H group (P<0.05).

CONCLUSION:

These results demonstrated that ecto-5'-nucleotidase activated by an overexpression of HSP72 attenuated ischemia-reperfusion injury in the rat myocardium. They suggest that ecto-5'-nucleotidase plays a role in the cardioprotective effects of HSP72 in rat hearts.

• Authors: T Sakaguchi, Y Sawa, M Kitakaze, K Suzuki, M Nishimura, Y Kaneda, H Matsuda
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 47 Issue 1 Pg. 74-80 (Jul 2000) ISSN: 0008-6363 [Print] England
• PMID: 10869532 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• HSP72 Heat-Shock Proteins
• Heat-Shock Proteins
• alpha,beta-methyleneadenosine 5'-diphosphate
• Adenosine Diphosphate
• Adenosine Triphosphatases
• ectoATPase

Topics

• Adenosine Diphosphate (analogs & derivatives, pharmacology)
• Adenosine Triphosphatases (antagonists & inhibitors, metabolism, physiology)
• Analysis of Variance
• Animals
• Blotting, Western
• Enzyme Activation
• Enzyme Inhibitors (pharmacology)
• Gene Expression
• HSP72 Heat-Shock Proteins
• Heat-Shock Proteins (genetics, metabolism)
• Male
• Myocardial Reperfusion Injury (metabolism)
• Perfusion
• Rats
• Rats, Sprague-Dawley
• Transfection