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Levosimendan Modulates Programmed Forms of Cell Death Through K(ATP) Channels and Nitric Oxide

Levosimendan Modulates Programmed Forms of Cell Death Through K(ATP) Channels and Nitric Oxide

Francesca Uberti, Philippe P Caimmi, Claudio Molinari, David Mary, Giovanni Vacca, Elena Grossini

J Cardiovasc Pharmacol. 2011 Feb;57(2):246-58.

PMID: 21107279

Abstract:

Levosimendan exerts cardioprotection through mitochondrial K(ATP) (mitoK(ATP)) channels opening. In addition, intracoronary levosimendan was found to modulate programmed forms of cell death by nitric oxide (NO) involvement. The aim of this study was to examine the role of mitoK(ATP) channels and NO in the effects of levosimendan on apoptosis/autophagy. In H9c2 cells treated with hydrogen peroxide apoptosis/autophagy, survival signaling, cell viability, mitochondrial membrane potential, and permeability transition pore opening were analyzed through Western blot and colorimetric and fluorescence assays. Pretreatment of H9c2 cells with levosimendan was able to counteract the oxidative injuries caused by hydrogen peroxide. The effects of levosimendan were potentiated by diazoxide and were similar to those elicited by the autophagic activator rapamycin. The autophagic inhibitor 3-methyladenine reduced the effects of levosimendan, whereas after the pan-caspases inhibitor N-Acetyl-Asp-Glu-Val-Asp-al (Z-VAD.FMK), cell survival and autophagy in response to levosimendan increased. Both the mitoK(ATP) channels inhibition and the NO synthase blocking attenuated the cardioprotection elicited by levosimendan. The results have shown that levosimendan protects H9c2 cells against oxidative injuries through the modulation of the interplay between autophagy and apoptosis and the activation of survival signaling. The mitoK(ATP) channels and NO may be involved in such cardioprotection through interference with mitochondrial functioning.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP169332609-B	N-Acetyl-Asp-Glu-Val-Asp-al		169332-60-9	Price

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