TY - JOUR T1 - Protective Role of Intracellular Zinc in Myocardial Ischemia/Reperfusion Is Associated with Preservation of Protein Kinase C Isoforms JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 517 LP - 525 DO - 10.1124/jpet.107.119644 VL - 321 IS - 2 AU - Gulnura Karagulova AU - Yuankun Yue AU - Abel Moreyra AU - Mohamed Boutjdir AU - Irina Korichneva Y1 - 2007/05/01 UR - http://jpet.aspetjournals.org/content/321/2/517.abstract N2 - The recent discovery of zinc signals and their essential role in the redox signaling network implies that zinc homeostasis and the function of zinc-containing proteins are probably altered as a result of oxidative stress, suggesting new targets for pharmacological intervention. We hypothesized that the level of intracellular labile zinc is changed in hearts subjected to ischemia/reperfusion (I/R) and investigated whether the maintenance of myocardial zinc status protected heart functions. Using fluorescent imaging, we demonstrated decreased levels of labile zinc in the I/R hearts. Phorbol 12-myristate 13-acetate, a known trigger of zinc release, liberated zinc ions in control hearts but failed to produce any increase in zinc levels in the I/R rat hearts. Adding the zinc ionophore pyrithione at reperfusion improved myocardial recovery up to 100% and reduced the incidence of arrhythmias more than 2-fold. This effect was dose-dependent, and high concentrations of zinc were toxic. Adding membrane-impermeable zinc chloride was ineffective. Hearts from rats receiving zinc pyrithione supplements in their diet fully recovered from I/R. The recovery was associated with the prevention of degradation of the two protein kinase C isoforms, δ and ϵ, during I/R. In conclusion, our results suggest a protective role of intracellular zinc in myocardial recovery from oxidative stress imposed by I/R. The data support the potential clinical use of zinc ionophores in the settings of acute redox stress in the heart. The American Society for Pharmacology and Experimental Therapeutics ER -