title: Nrf2-regulated antioxidant response is activated by protein kinase C in postconditioned rat hearts.
abstract: Postconditioning (PostC) activates endogenous protective mechanisms that contend against reperfusion injury. Nevertheless, although PostC efficiency in both experimental studies and clinical trials has been demonstrated, a complete picture of the interacting mechanisms, particularly the relationship between kinase signaling and redox maintenance, is still lacking. To unravel such association, in this work we focus on the participation of protein kinase C (PKC) and the transcription factor nuclear factor E2-related factor 2 (Nrf2) in the cardioprotective response elicited by PostC. PostC was performed in an in vivo rat model by applying three repetitive cycles of ischemia and reperfusion (10 s each), followed by evaluation of heart function and infarct size measurements. PKC activation and Nrf2 phosphorylation were evaluated after 10 min of reperfusion, whereas Nrf2 activity and the content and activities of Nrf2-regulated antioxidant proteins were evaluated after 60 min of reperfusion in PostC hearts. Maintenance of heart function and diminution in infarct size concurred with PKC activation and Nrf2 phosphorylation. PKC inhibition diminished Nrf2 phosphorylation and transcriptional activity in association with diminished levels and activities of Nrf2-regulated antioxidant proteins. In conclusion, this study proposes that the novel pathway PKC/Nrf2 participates in the long-term protective mechanisms induced by PostC application by maintaining the antioxidant defense system.
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology I. Ch., Mexico City 14080, DF, Mexico.
authors.forename: Mabel
authors.initials: M
authors.lastname: Buelna-Chontal
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology I. Ch., Mexico City 14080, DF, Mexico.
authors.forename: José-Guadalupe
authors.initials: JG
authors.lastname: Guevara-Chávez
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology I. Ch., Mexico City 14080, DF, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Silva-Palacios
authors.affiliation: Biology Department, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City, DF, Mexico.
authors.forename: Omar-Noel
authors.initials: ON
authors.lastname: Medina-Campos
authors.affiliation: Biology Department, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City, DF, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.affiliation: Department of Cardiovascular Biomedicine, National Institute of Cardiology I. Ch., Mexico City 14080, DF, Mexico. Electronic address: azazuetam@yahoo.com.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zazueta
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019610:Cytoprotection; D006321:Heart / Q000502:physiology*; D006334:Heart Function Tests; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D015533:Transcriptional Activation
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D011493:Protein Kinase C
keywords: Cardioprotection; Free radicals; Nrf2; PKC; Postconditioning; ROS