Persulfidation of mitoKv7.4 channels contributes to the cardioprotective effects of the H2S-donor Erucin against ischemia/reperfusion injury.

Abstract

BACKGROUND:

Hydrogen sulfide (H2S) is a gasotransmitter deeply involved in cardiovascular homeostasis and implicated in the myocardial protection against ischemia/reperfusion. The post-translational persulfidation of cysteine residues has been identified as the mechanism through which H2S regulates a plethora of biological targets. Erucin (ERU) is an isothiocyanate produced upon hydrolysis of the glucosinolate glucoerucin, presents in edible plants of Brassicaceae family, such as Eruca sativa Mill., and it has emerged as a slow and long-lasting H2S-donor.

AIM:

In this study the cardioprotective profile of ERU has been investigated and the action mechanism explored, focusing on the possible role of the recently identified mitochondrial Kv7.4 (mitoKv7.4) potassium channels.

RESULTS:

Interestingly, ERU showed to release H2S and concentration-dependently protected H9c2 cells against H2O2-induced oxidative damage. Moreover, in in vivo model of myocardial infarct ERU showed protective effects, reducing the extension of ischemic area, the levels of troponin I and increasing the amount of total AnxA1, as well as co-related inflammatory outcomes. Conversely, the pre-treatment with XE991, a blocker of Kv7.4 channels, abolished them. In isolated cardiac mitochondria ERU exhibited the typical profile of a mitochondrial potassium channels opener, in particular, this isothiocyanate produced a mild depolarization of mitochondrial membrane potential, a reduction of calcium accumulation into the matrix and finally a flow of potassium ions. Finally, mitoKv7.4 channels were persulfidated in ERU-treated mitochondria.

CONCLUSIONS:

ERU modulates the cardiac mitoKv7.4 channels and this mechanism may be relevant for cardioprotective effects.

• Authors: L Testai, R Montanaro, L Flori, E Pagnotta, V Vellecco, E Gorica, L Ugolini, L Righetti, V Brancaleone, M Bucci, E Piragine, A Martelli, L Di Cesare Mannelli, C Ghelardini, V Calderone
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 215 Pg. 115728 (09 2023) ISSN: 1873-2968 [Electronic] England
• PMID: 37524208 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• erucin
• Hydrogen Peroxide
• Hydrogen Sulfide
• isothiocyanic acid
• Isothiocyanates
• Potassium Channels

Topics

• Humans
• Hydrogen Peroxide (pharmacology)
• Hydrogen Sulfide (pharmacology, metabolism)
• Isothiocyanates (pharmacology)
• Myocardial Reperfusion Injury (drug therapy, prevention & control)
• Potassium Channels
• Mitochondria, Heart