Increased protein S-nitrosylation in mitochondria: a key mechanism of exercise-induced cardioprotection

Autor: Doria Boulghobra, Mathilde Dubois, Béatrice Alpha-Bazin, Florence Coste, Maxime Olmos, Sandrine Gayrard, Isabelle Bornard, Gregory Meyer, Jean-Charles Gaillard, Jean Armengaud, Cyril Reboul
Přispěvatelé: EA4278 Laboratoire de Pharm-Ecologie Cardiovasculaire (LaPEC), Avignon Université (AU), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Pathologie Végétale (PV), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), PhD grant from SFR Tersys, PhD mobility grant from the Groupe de Réflexion sur la Recherche Cardiovasculaire, ANR-21-CE14-0058,NitrosoCard,S-nitrosylation des myofilaments cardiaques : conséquences sur l’adaptation du coeur au stress mécanique, ANR-21-CE14-0058,NitrosoCard,S-nitrosylation des myofilaments cardiaques : conséquences sur l'adaptation du cœur au stress mécanique(2021)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Basic Research in Cardiology
Basic Research in Cardiology, Springer Verlag, 2021, 116 (1), pp.66. ⟨10.1007/s00395-021-00906-3⟩
Basic Research in Cardiology, 2021, 116 (1), pp.66. ⟨10.1007/s00395-021-00906-3⟩
ISSN: 0300-8428
1435-1803
Popis: International audience; Endothelial nitric oxide synthase (eNOS) activation in the heart plays a key role in exercise-induced cardioprotection during ischemia-reperfusion, but the underlying mechanisms remain unknown. We hypothesized that the cardioprotective effect of exercise training could be explained by the re-localization of eNOS-dependent nitric oxide (NO)/S-nitrosylation signaling to mitochondria. By comparing exercised (5 days/week for 5 weeks) and sedentary Wistar rats, we found that exercise training increased eNOS level and activation by phosphorylation (at serine 1177) in mitochondria, but not in the cytosolic subfraction of cardiomyocytes. Using confocal microscopy, we confirmed that NO production in mitochondria was increased in response to H 2 O 2 exposure in cardiomyocytes from exercised but not sedentary rats. Moreover, by S-nitrosoproteomic analysis, we identified several key S-nitrosylated proteins involved in mitochondrial function and cardioprotection. In agreement, we also observed that the increase in Ca 2+ retention capacity by mitochondria isolated from the heart of exercised rats was abolished by exposure to the NOS inhibitor L-NAME or to the reducing agent ascorbate, known to denitrosylate proteins. Pre-incubation with ascorbate or L-NAME also increased mitochondrial reactive oxygen species production in cardiomyocytes from exercised but not from sedentary animals. We confirmed these results using isolated hearts perfused with L-NAME before ischemia-reperfusion. Altogether, these results strongly support the hypothesis that exercise training increases eNOS/NO/S-nitrosylation signaling in mitochondria, which might represent a key mechanism of exercise-induced cardioprotection.
Databáze: OpenAIRE
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