Liem 2008 Transl Res

Liem D, Manintveld O, Schoonderwoerd K, McFalls E, Heinen A, Verdouw P, Sluiter W, Duncker D (2008) Ischemic preconditioning modulates mitochondrial respiration, irrespective of the employed signal transduction pathway. Transl Res 151: 17-26.

» PMID: 18061124

Liem D, Manintveld O, Schoonderwoerd K, McFalls E, Heinen A, Verdouw P, Sluiter W, Duncker D (2008) Transl Res

Abstract: We tested in the in vivo rat heart the hypothesis that although ischemic preconditioning can employ different signal transduction pathways, these pathways converge ultimately at the level of the mitochondrial respiratory chain. Infarct size produced by a 60-min coronary artery occlusion (69% ± 2% of the area at risk) was limited by a preceding 15-min coronary occlusion (48% ± 4%). Cardioprotection by this stimulus was triggered by adenosine receptor stimulation, which was followed by protein kinase C and tyrosine kinase activation and then mitochondrial K⁺_ATP-channel opening. In contrast, cardioprotection by 3 cycles of 3-min coronary occlusions (infarct size 27% ± 5% of the area at risk) involved the release of reactive oxygen species, which was followed by protein kinase C and tyrosine kinase activation, but was independent of adenosine receptor stimulation and K+ATP-channel activation. However, both pathways decreased respiratory control index (RCI; state-3/state-2, using succinate as complex-II substrate) from 3.1 ± 0.2 in mitochondria from sham-treated hearts to 2.4 ± 0.2 and 2.5 ± 0.1 in hearts subjected to a single 15-min and triple 3-min coronary occlusions, respectively (both P < 0.05). The decreases in RCI were due to an increase in state-2 respiration, whereas state-3 respiration was unchanged. Abolition of cardioprotection by blockade of either signal transduction pathway was paralleled by a concomitant abolition of mitochondrial uncoupling. These observations are consistent with the concept that mild mitochondrial uncoupling contributes to infarct size limitation by various ischemic preconditioning stimuli, despite using different signal transduction pathways. In conclusion, in the in vivo rat heart, different ischemic preconditioning (IPC) stimuli can activate highly different signal transduction pathways, which seem to converge at the level of the mitochondria where they increase state-2 respiration.

• O2k-Network Lab: NL Rotterdam Sluiter W

Labels:

Stress:Ischemia-Reperfusion; Preservation"Ischemia-Reperfusion; Preservation" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.  Organism: Rat  Tissue;cell: Heart  Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.  Enzyme: Complex II; Succinate Dehydrogenase"Complex II; Succinate Dehydrogenase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.  Regulation: Substrate; Glucose; TCA Cycle"Substrate; Glucose; TCA Cycle" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.  Coupling state: OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property. 

HRR: Oxygraph-2k