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Pharmaceuticals 2015, 8(3), 474-482; doi:10.3390/ph8030474

UCP2 Modulates Cardioprotective Effects of Ru360 in Isolated Cardiomyocytes during Ischemia

Department of Internal Medicine II, Paracelsus Medical University, Salzburg 5020, Austria
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Author to whom correspondence should be addressed.
Academic Editor: Jean Jacques Vanden Eynde
Received: 4 June 2015 / Revised: 17 July 2015 / Accepted: 29 July 2015 / Published: 4 August 2015
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Abstract

Introduction: Ruthenium 360 (Ru360) has been shown to induce cardioprotective mechanisms in perfused hearts. The agent is a specific blocker of the main cardiac mitochondrial uptake mechanism, the mitochondrial calcium uniporter (MCU). UCP2, a mitochondrial membrane protein, which influences cardiac ROS formation was reported to interact with the MCU. Methods: To prove whether Ru360 affects ischemic cell injury on the singular cell level, cell viability (CV) in isolated cardiomyocytes from wild type mice (WT) was measured in a model of pelleting hypoxia (PH). To explore a possible influence of UCP2 on cellular survival, as well as on Ru360 function, cardiomyocytes from UCP2−/− mice were investigated. Results: During PH, Ru360 significantly improved CV in WT cardiomyocytes (Control 26.32% ± 1.58% vs. PH 13.60% ± 1.20% vs. PH+Ru360 19.98% ± 0.98%, n = 6; p < 0.05). No differences in the rate of apoptosis were observed in UCP2−/− vs. WT. In UCP2−/− cardiomyocytes, Ru360 reduced the rate of cell death. However, the effect was less pronounced compared to WT cardiomyocytes. Conclusion: Ru360 significantly reduces hypoxic cell injury by preventing single cell apoptosis in WT cardiomyoctes. UCP2 does not affect cell survival in hypoxic cardiomyocytes, but it might modulate cardioprotective effects of Ru360 during ischemia. View Full-Text
Keywords: mitochondrial calcium uniporter; ruthenium; UCP2; ischemia; cardiomyocytes; cardioprotection mitochondrial calcium uniporter; ruthenium; UCP2; ischemia; cardiomyocytes; cardioprotection
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Motloch, L.J.; Reda, S.; Wolny, M.; Hoppe, U.C. UCP2 Modulates Cardioprotective Effects of Ru360 in Isolated Cardiomyocytes during Ischemia. Pharmaceuticals 2015, 8, 474-482.

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