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

• DOI: 10.1016/j.bcp.2023.115728
• Publication Date: 2023-07-29T14:55:32Z
• 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 Mann...; C. Ghelardini; V. Calderone
• Keywords: Eruca; Nicorandil; Ischemic Preconditioning

Hydrogen sulfide (H2S) is a gasotransmitter deeply involved in cardiovascular homeostasis and implicated the myocardial protection against ischemia/reperfusion. The post-translational persulfidation of cysteine residues has been identified as mechanism through which H2S regulates plethora biological targets. Erucin (ERU) an isothiocyanate produced upon hydrolysis glucosinolate glucoerucin, presents edible plants Brassicaceae family, such Eruca sativa Mill., it emerged slow long-lasting H2S-donor. In this study cardioprotective profile ERU investigated action explored, focusing on possible role recently mitochondrial Kv7.4 (mitoKv7.4) potassium channels. Interestingly, showed to release concentration-dependently protected H9c2 cells H2O2-induced oxidative damage. Moreover, vivo model infarct protective effects, reducing extension ischemic area, levels troponin I increasing amount total AnxA1, well co-related inflammatory outcomes. Conversely, pre-treatment with XE991, blocker channels, abolished them. isolated cardiac mitochondria exhibited typical channels opener, particular, mild depolarization membrane potential, reduction calcium accumulation into matrix finally flow ions. Finally, mitoKv7.4 were persulfidated ERU-treated mitochondria. modulates may be relevant for effects.