title: Effects of the AMP-activated protein kinase inhibitor compound C on the postconditioned rat heart.
abstract: Ischemic postconditioning (IPOC) protects the myocardium from ischemic-reperfusion injury, improving functional recovery and cell viability. This protection is concurrent with stimulation of glycogen breakdown, increased mitochondrial ATP synthesis and content, maintenance of reduced-to-oxidized glutathione ratio (GSH/GSSG), and decreased oxidative damage. The present study's objective was to assess whether these effects are associated with increased resistance to mitochondrial permeability transition pore (MPTP) opening. The effects of the AMP-activated protein kinase (AMPK) inhibitor, compound C (CC), were measured to investigate association with AMPK. Mitochondria removed from postconditioned hearts required higher calcium levels to induce MPTP opening. Improved functional recovery, increased glycogen mobilization, maintenance of the GSH/GSSG ratio, decreased oxidative damage, and increased resistance to MPTP opening were abrogated when the hearts were postconditioned in the presence of CC, without affecting preservation of cell viability. Although AMPK appears to play a role in IPOC, it would not be the major cellular mediator.
authors.affiliation: Physiology Unit, Department of Biological Sciences, School of Pharmacy and Biochemistry, Universidad de Buenos Aires and IQUIMEFA-CONICET, Buenos Aires, Argentina.
authors.forename: R
authors.initials: R
authors.lastname: Hermann
authors.forename: M G
authors.initials: MG
authors.lastname: Marina Prendes
authors.forename: M E
authors.initials: ME
authors.lastname: Torresin
authors.forename: D
authors.initials: D
authors.lastname: Vélez
authors.forename: E A
authors.initials: EA
authors.lastname: Savino
authors.forename: A
authors.initials: A
authors.lastname: Varela
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D057775:Ischemic Postconditioning; D008929:Mitochondria, Heart / Q000187:drug effects*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D018384:Oxidative Stress; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011720:Pyrazoles; D011743:Pyrimidines; C516138:dorsomorphin; D055372:AMP-Activated Protein Kinases; D005978:Glutathione; D019803:Glutathione Disulfide