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Biapigenin Modulates the Activity of the Adenine Nucleotide Translocator in Isolated Rat Brain Mitochondria

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Abstract

In this study, we investigated the effects of biapigenin, a biflavone present in the extracts of Hypericum perforatum, in rat brain mitochondrial bioenergetics and calcium homeostasis. We found that biapigenin significantly decreased adenosine diphosphate (ADP)-induced membrane depolarization and increased repolarization (by 68 and 37%, respectively). These effects were blocked by atractyloside and bongkrekic acid, but not oligomycin. In the presence of biapigenin, an ADP-stimulated state 3 respiration was still noticeable, which did not happen in the presence of adenine nucleotide translocator (ANT) inhibitors. Taking in consideration the relevance of the ANT in the modulation of the mitochondrial permeability transition pore (mPTP), mitochondrial calcium homeostasis was evaluated alone or in the presence of biapigenin. We found that biapigenin reduces mitochondrial calcium retention by increasing calcium efflux, an effect that was blocked by ADP plus oligomycin, an efficient blocker of the mPTP in brain mitochondria. Taken together, the results in this article suggest that biapigenin modulates mPTP opening, possibly by modulating ANT function, contributing for enhanced mitochondrial calcium efflux, thereby reducing calcium burden and contributing for neuroprotection against excitotoxicity.

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Abbreviations

ΔΨm :

Mitochondrial transmembrane electric potential

ANT:

Adenosine nucleotide translocator

CsA:

Cyclosporin A

FCCP:

Carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone

mPTP:

Mitochondrial permeability transition pore

TPP:

Tetraphenylphosphonium-chloride

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Acknowledgment

We acknowledge the Portuguese Foundation for Science and Technology and FEDER for support, PhD grant SFRH/BD/13488/2003, and research projects POCI/SAU-NEU/58492/2004.

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Authors and Affiliations

  1. Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Bruno A. Silva, Paulo J. Oliveira, Armando Cristóvão & João O. Malva

  2. Faculty of Medicine, Institute of Biochemistry, University of Coimbra, 3004-504, Coimbra, Portugal

    João O. Malva

  3. Department of Zoology, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal

    Armando Cristóvão

  4. Department of Biology, Centro de Investigação e de Tecnologias Agro-Ambientais e Biológicas (CITAB), University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal

    Bruno A. Silva & Alberto C. P. Dias

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  1. Bruno A. Silva
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  2. Paulo J. Oliveira
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Correspondence to João O. Malva.

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Silva, B.A., Oliveira, P.J., Cristóvão, A. et al. Biapigenin Modulates the Activity of the Adenine Nucleotide Translocator in Isolated Rat Brain Mitochondria. Neurotox Res 17, 75–90 (2010). https://doi.org/10.1007/s12640-009-9082-5

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  • DOI: https://doi.org/10.1007/s12640-009-9082-5

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