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  • Title: Ecto-5'-nucleotidase plays a role in the cardioprotective effects of heat shock protein 72 in ischemia-reperfusion injury in rat hearts.
    Author: Sakaguchi T, Sawa Y, Kitakaze M, Suzuki K, Nishimura M, Kaneda Y, Matsuda H.
    Journal: Cardiovasc Res; 2000 Jul; 47(1):74-80. PubMed ID: 10869532.
    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.
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