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Pharmacological preconditioning protects from ischemia/reperfusion‐induced apoptosis by modulating Bcl‐xL expression through a ROS‐dependent mechanism
Author(s) -
Rozier Romain,
Paul Rachel,
Madji Hounoum Blandine,
Villa Elodie,
Mhaidly Rana,
Chiche Johanna,
Verhoeyen Els,
Marchetti Sandrine,
Vandenberghe Ashaina,
Raucoules Marc,
Carles Michel,
Ricci JeanEhrland
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15675
Subject(s) - reperfusion injury , apoptosis , cardioprotection , pharmacology , ischemia , ischemic preconditioning , signal transduction , medicine , protein kinase b , microbiology and biotechnology , chemistry , biology , biochemistry
Myocardial ischemia/reperfusion (I/R) injury is a frequent perioperative threat, with numerous strategies developed to limit and/or prevent it. One interesting axis of research is the anesthetic preconditioning (APc) agent’s hypothesis (such as sevoflurane, SEV). However, APc’s mode of action is still poorly understood and volatile anesthetics used as preconditioning agents are often not well suited in clinical practice. Here, in vitro using H9C2 cells lines (in myeloblast state or differentiated toward cardiomyocytes) and in vivo in mice, we identified that SEV‐induced APc is mediated by a mild induction of reactive oxygen species (ROS) that activates Akt and induces the expression of the anti‐apoptotic protein B‐cell lymphoma‐extra large (Bcl‐xL), therefore protecting cardiomyocytes from I/R‐induced death. Furthermore, we extended these results to human cardiomyocytes (derived from induced pluripotent stem ‐ IPS ‐ cells). Importantly, we demonstrated that this protective signaling pathway induced by SEV could be stimulated using the antidiabetic agent metformin (MET), suggesting the preconditioning properties of MET. Altogether, our study identified a signaling pathway allowing APc of cardiac injuries as well as a rational for the use of MET as a pharmacological preconditioning agent to prevent I/R injuries.