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Effect of Ischemic Preconditioning on Mitochondrial Dysfunction and Mitochondrial P53 Translocation after Transient Global Cerebral Ischemia in Rats

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Abstract

Transient global brain ischemia induces dysfunctions of mitochondria including disturbance in mitochondrial protein synthesis and inhibition of respiratory chain complexes. Due to capacity of mitochondria to release apoptogenic proteins, ischemia-induced mitochondrial dysfunction is considered to be a key event coupling cerebral blood flow arrest to neuronal cell death. Ischemic preconditioning (IPC) represents an important phenomenon of adaptation of central nervous system (CNS) to sub-lethal short-term ischemia, which results in increased tolerance of CNS to the lethal ischemia. In this study we have determined the effect of ischemic preconditioning on ischemia/reperfusion-associated inhibition of mitochondrial protein synthesis and activity of mitochondrial respiratory chain complexes I and IV in the hippocampus of rats. Global brain ischemia was induced by 4-vessel occlusion in duration of 15 min. Rats were preconditioned by 5 min of sub-lethal ischemia and 2 days later, 15 min of lethal ischemia was induced. Our results showed that IPC affects ischemia-induced dysfunction of hippocampal mitochondria in two different ways. Repression of mitochondrial translation induced during reperfusion of the ischemic brain is significantly attenuated by IPC. Slight protective effect of IPC was documented for complex IV, but not for complex I. Despite this, protective effect of IPC on ischemia/reperfusion-associated changes in integrity of mitochondrial membrane and membrane proteins were observed. Since IPC exhibited also inhibitory effect on translocation of p53 to mitochondria, our results indicate that IPC affects downstream processes connecting mitochondrial dysfunction to neuronal cell death.

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Abbreviations

BSA:

Bovine serum albumin

IPC:

Ischemic preconditioning

PAGE:

Polyacrylamide gel electrophoresis

SDS:

Sodium dodecyl sulphate

TBS-T:

Tris-buffered saline with addition of 0.05% of Tween 20

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Acknowledgements

This work was supported by the Ministry of Education of Slovak Republic (grant VEGA 1/1192/04 to P.R.). We would like to thank Zdenka Cetlova and Jolana Bencatova for excellent technical assistance

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  1. Institute of Biochemistry, Jessenius Faculty of Medicine, Comenius University, Mala Hora 4, Martin, 03601, Slovak Republic

    Peter Racay, Zuzana Tatarkova, Anna Drgova, Peter Kaplan & Dusan Dobrota

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  1. Peter Racay
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  2. Zuzana Tatarkova
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Correspondence to Peter Racay.

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Racay, P., Tatarkova, Z., Drgova, A. et al. Effect of Ischemic Preconditioning on Mitochondrial Dysfunction and Mitochondrial P53 Translocation after Transient Global Cerebral Ischemia in Rats. Neurochem Res 32, 1823–1832 (2007). https://doi.org/10.1007/s11064-007-9437-3

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  • DOI: https://doi.org/10.1007/s11064-007-9437-3

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