Borutaite 2013 Abstract MiP2013

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Borutaite V, Jablonskiene G, Arandarcikaite O (2013) Mitochondrial response to heart and brain ischemia. Mitochondr Physiol Network 18.08.
Link:
Vilma Borutaite
MiP2013, Book of Abstracts Open Access

Borutaite V, Jablonskiene G, Arandarcikaite O (2013)

Event: MiPNet18.08_MiP2013

We compared three models of cerebral ischemia in piglets – unilateral and bilateral carotid artery occlusion as well as bilateral occlusion with hypotension for 3 h. These surgical procedures produced different effects on microcirculation which were accompanied by the gradual decline in the activity of mitochondrial oxidative phosphorylation. We found that LEAK respiration (measured in the presence of pyruvate plus malate but without ADP) was not affected by ischemia in any experimental model. The OXPHOS capacity with pyruvate+malate as substrates decreased by 20% and 80% compared to the control level after bilateral carotid artery occlusion and bilateral carotid artery occlusion plus hypotension, respectively, resulting in the decrease of respiratory control index. OXPHOS capacity with succinate as substrate remained constant after unilateral carotid artery occlusion or bilateral carotid artery occlusion but decreased by 50% after bilateral carotid artery occlusion and hypotension. No loss of cytochrome c from mitochondria was observed in any model of cerebral ischemia. This suggests that damage to Complex I of the mitochondrial respiratory system is the primary target of ischemic insult and may lead to subsequent delayed neuronal death in piglet model of global cerebral ischemia.

In the in vitro model of rat global brain ischemia, mitochondrial OXPHOS activity with pyruvate plus malate and to a lesser extent with succinate was decreased after 30 min ischemia. OXPHOS activity with both substrates decreased further during 60-120 min period. This inhibition was not reversed in the presence of added cytochrome c suggesting that inhibition of OXPHOS was not caused by the loss of cytochrome c. Measurements of mitochondrial content of cytochrome c confirmed this as there was no change in cytochrome c levels during 30-120 min ischemic period. These findings are in contrast to reported previously for heart ischemia where it was found that the loss of cytochrome c from mitochondria is the earliest event in ischemic mitochondrial damage leading to caspase activation and cell death [1].

In conclusion, our data suggest that brain and heart ischemia causes mitochondrial damage, however, the mechanisms involved are different: Ischemic damage to heart mitochondria is primarily related to opening of mitochondrial permeability transition pore and the release of cytochrome c, whereas during brain ischemia the earliest event is inhibition of Complex I.

Keywords: oxidate phosphrylation, stroke

O2k-Network Lab: LT Kaunas Borutaite V


Labels: MiParea: Respiration, Comparative MiP;environmental MiP  Pathology: Neurodegenerative  Stress:Ischemia-reperfusion, Permeability transition  Organism: Pig, Rat  Tissue;cell: Heart, Nervous system  Preparation: Isolated mitochondria  Enzyme: Complex I, Complex IV;cytochrome c oxidase  Regulation: Cyt c  Coupling state: LEAK, OXPHOS  Pathway: N, S  HRR: Oxygraph-2k 

MiP2013, S05 

Affiliations and author contributions

Institute of Neurosciences, Lithuanian University of Health Sciences, Kaunas, Lithuania. - Email: vilmante.borutaite@lsmuni.lt


References

  1. Borutaite V, Jekabsone A, Morkuniene R, Brown GC (2003) Inhibition of mitochondrial permeability transition prevents mitochondrial dysfunction, cytochrome c release and apoptosis induced by heart ischemia. J Mol Cell Cardiol 35:357-66.