title: Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning.
abstract: Altered expression of mitochondrial electron transport proteins has been shown in early preconditioned myocardial tissue. We wished to determine whether these alterations persist in the Second Window of Protection (SWOP) and if so, whether a favorable energetic state is facilitated during subsequent ischemia. Fourteen pigs underwent a SWOP protocol with ten 2-minute balloon inflations in the LAD artery, each separated by 2 minutes reperfusion. Twenty-four hours later, mitochondria were isolated from SWOP and SHAM pig hearts and analyzed for uncoupling protein (UCP)-2 content by western blot analysis, proteomic changes by iTRAQ(®) and respiration by an oxygen electrode. In parallel in vivo studies, high-energy nucleotides were obtained by transmural biopsy from anesthetized SWOP and SHAM pigs at baseline and during sustained low-flow ischemia. Compared with SHAM mitochondria, ex vivo SWOP heart tissue demonstrated increased expression of UCP-2, Complex IV (cytochrome c oxidase) and Complex V (ATPase) proteins. In comparison with SHAM pigs during in vivo conditions, transmural energetics in SWOP hearts, as estimated by the free energy of ATP hydrolysis (ΔG(0)), were similar at baseline but had decreased by the end of low-flow ischemia (-57.0 ± 2.1 versus -51.1 ± 1.4 kJ/mol; P < 0.05). In conclusion, within isolated mitochondria from preconditioned SWOP hearts, UCP-2 is increased and in concert with enhanced Complex IV and V proteins, imparts a favorable energetic state during low-flow ischemia. These data support the notion that mitochondrial adaptations that may reduce oxidant damage do not reduce the overall efficiency of energetics during sustained oxygen deprivation.
authors.affiliation: Cardiology and Cardiothoracic Surgery Sections, VA Medical Center, University of Minnesota, Minneapolis, MN 55417, USA.
authors.forename: Jesús A
authors.initials: JA
authors.lastname: Cabrera
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ziemba
authors.forename: Robert
authors.initials: R
authors.lastname: Colbert
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Anderson
authors.forename: Willem
authors.initials: W
authors.lastname: Sluiter
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: Tammy A
authors.initials: TA
authors.lastname: Butterick
authors.forename: Joseph
authors.initials: J
authors.lastname: Sikora
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Ward
authors.forename: Rosemary F
authors.initials: RF
authors.lastname: Kelly
authors.forename: Edward O
authors.initials: EO
authors.lastname: McFalls
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D008565:Membrane Proteins / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism*; D013552:Swine; D000071246:Uncoupling Protein 2
chemical_list: D002352:Carrier Proteins; D045222:Electron Transport Chain Complex Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000071246:Uncoupling Protein 2; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; C020439:oligomycin sensitivity-conferring protein