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Is zinc important for the cardioprotective effect of ischemic postconditioning?
Author(s) -
Xu Zhelong,
Zhou Juan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb612
Subject(s) - cardioprotection , zinc , ischemia , reperfusion injury , pharmacology , intracellular , chemistry , medicine , biochemistry , organic chemistry
Zinc loss may contribute the pathogenesis of myocardial ischemia/reperfusion injury. We aimed to test if ischemic postconditioning protects the heart from reperfusion injury by preventing cellular zinc loss. Isolated rat hearts were subjected to 30 min regional ischemia followed by 2 h of reperfusion. Postconditioning was elicited by six cycles of 10 second reperfusion and 10 seconds ischemia. Intracellular zinc levels were measured with inductively coupled plasma optical spectroscopy (ICPOES). Upon reperfusion cytosolic zinc levels were dramatically decreased but this was prevented by postconditioning, indicating that postconditioning can prevent reperfusion‐induced zinc loss. In agreement with these observations, the cardioprotective effect of postconditioning was reversed by the zinc chelator N,N,N′,N′‐tetrakis‐(2‐pyridylmethyl) ethylenediamine (TPEN), and exogenous zinc given at reperfusion mimicked the effect of postconditioning, suggesting that postconditioning induces cardioprotection by preventing zinc loss. Finally, postconditioning enhanced phosphorylation of Akt, ERK, and GSK‐3β upon reperfusion, and these effects of postconditioning were inhibited by TPEN, indicating that zinc may mediate the cardioprotective effect of postconditioning by activating the RISK pathway. In conclusion, these data suggest that postconditioning may protect the heart by maintaining intracellular zinc homeostasis and activation of the RISK pathway may account for zinc‐mediated cardioprotection of postconditioning.