title: Gsk-3β inhibitors mimic the cardioprotection mediated by ischemic pre- and postconditioning in hypertensive rats.
abstract: The aim of this study was to examine the effects of GSK-3 β inhibitors compared with PRE and POS in spontaneously hypertensive rats (SHR). Isolated hearts were submitted to the following protocols: IC: 45 min global ischemia (GI) and 1-hour reperfusion (R); PRE: a cycle of 5 min GI and 10 minutes of R prior to 45 min GI; POS: three cycles of 30 sec GI/30 sec R at the start of R. Other hearts received lithium chloride (LiCl) or indirubin-3'-monoxime,5-iodo-(IMI) as GSK-3 β inhibitors. All interventions reduced the infarct size observed in IC group. The expressions of P-GSK-3 β and P-Akt decreased in IC and were restored after PRE, POS, and GSK-3 β inhibitors treatments. An increase of cytosolic MnSOD activity and lipid peroxidation and a decrease of GSH content observed in IC hearts were attenuated in PRE, POS, and LiCl or IMI treatments. An increase of P-GSK-3 β /VDAC physical association and a partial recovery of mitochondrial permeability were also detected after interventions. These data show that, in SHR hearts, GSK-3 β inhibitors mimic the cardioprotection afforded by PRE and POS and suggest that a decrease in mitochondrial permeability mediated by P-GSK-3 β /VDAC interaction is a crucial event.
authors.affiliation: Fellowship of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, 1900, La Plata, Buenos Aires, Argentina.
authors.forename: Luisa F
authors.initials: LF
authors.lastname: González Arbeláez
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Pérez Núñez
authors.forename: Susana M
authors.initials: SM
authors.lastname: Mosca
mesh_terms: D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D007211:Indoles / Q000008:administration & dosage; D057775:Ischemic Postconditioning; D019194:Ischemic Preconditioning; D015227:Lipid Peroxidation / Q000235:genetics; D018021:Lithium Chloride / Q000008:administration & dosage; D009924:Organ Culture Techniques / Q000379:methods*; D010091:Oximes / Q000008:administration & dosage; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000235:genetics*
chemical_list: D007211:Indoles; D010091:Oximes; C474021:indirubin-3'-monoxime; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride