Cardioprotective pathways during reperfusion: focus on redox signaling and other modalities of cell signaling.
Post-ischemic reperfusion may result in reactive oxygen species (ROS) generation, reduced availability of nitric oxide (NO•), Ca(2+)overload, prolonged opening of mitochondrial permeability transition pore, and other processes contributing to cell death, myocardial infarction, stunning, and arrhythmias. With the discovery of the preconditioning and postconditioning phenomena, reperfusion injury has been appreciated as a reality from which protection is feasible, especially with postconditioning, which is under the control of physicians. Potentially cooperative protective signaling cascades are recruited by both pre- and postconditioning. In these pathways, phosphorylative/dephosphorylative processes are widely represented. However, cardioprotective modalities of signal transduction also include redox signaling by ROS, S-nitrosylation by NO• and derivative, S-sulfhydration by hydrogen sulfide, and O-linked glycosylation with beta-N-acetylglucosamine. All these modalities can interact and regulate an entire pathway, thus influencing each other. For instance, enzymes can be phosphorylated and/or nitrosylated in specific and/or different site(s) with consequent increase or decrease of their specific activity. The cardioprotective signaling pathways are thought to converge on mitochondria, and various mitochondrial proteins have been identified as targets of these post-transitional modifications in both pre- and postconditioning.
Pagliaro
Pasquale
P
Department of Clinical and Biological Sciences, Università di Torino, Regione Gonzole 10, Orbassano, Turin, Italy. pasquale.pagliaro@unito.it
Moro
Francesca
F
Tullio
Francesca
F
Perrelli
Maria-Giulia
MG
Penna
Claudia
C
D000818:Animals; D006801:Humans; D057775:Ischemic Postconditioning / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D009569:Nitric Oxide