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Agmatine prevents the Ca2+-dependent induction of permeability transition in rat brain mitochondria

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Abstract

The arginine metabolite agmatine is able to protect brain mitochondria against the drop in energy capacity by the Ca2+-dependent induction of permeability transition (MPT) in rat brain mitochondria. At normal levels, the amine maintains the respiratory control index and ADP/O ratio and prevents mitochondrial colloid-osmotic swelling and any electrical potential (ΔΨ) drop. MPT is due to oxidative stress induced by the interaction of Ca2+ with the mitochondrial membrane, leading to the production of hydrogen peroxide and, subsequently, other reactive oxygen species (ROS) such as hydroxyl radicals. This production of ROS induces oxidation of sulfhydryl groups, in particular those of two critical cysteines, most probably located on adenine nucleotide translocase, and also oxidation of pyridine nucleotides, resulting in transition pore opening. The protective effect of agmatine is attributable to a scavenging effect on the most toxic ROS, i.e., the hydroxyl radical, thus preventing oxidative stress and consequent bioenergetic collapse.

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Abbreviations

ADC:

Arginine decarboxylase

AGM:

Agmatine

BKA:

Bongkrekic acid

CsA:

Cyclosporin A

ΔΨ:

Electrical transmembrane potential

\( \Updelta \mu_{{{\text{H}}^{ + } }} \) :

Transmembrane electrochemical gradient

DMO:

5,5′-dimethyl-oxazolidine-2,4-dione

DTE:

Dithioerythritol

MPT:

Mitochondrial permeability transition

NEM:

N-Ethylmaleimide

NOS:

Nitric oxide-synthase

ODC:

Ornithine decarboxylase

RBM:

Rat brain mitochondria

RCI:

Respiratory control index

RKM:

Rat kidney mitochondria

RLM:

Rat liver mitochondria

ROS:

Reactive oxygen species

SSAT:

Spermidine/spermine-N 1-acetyltransferase

TPP+ :

Tetraphenylphosphonium

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Authors and Affiliations

  1. Department of Biological Chemistry, University of Padua, Viale G. Colombo, 3, 35121, Padua, Italy

    V. Battaglia, S. Grancara & A. Toninello

  2. Division of Nephrology-Hypertension, Department of Medicine, The Veterans Administration San Diego Healthcare System, University of California, San Diego, CA, USA

    J. Satriano

  3. Department of Biochemical Sciences, SAPIENZA, University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy

    S. Saccoccio & E. Agostinelli

  4. CNR, Biology and Molecular Pathology Institutes, Piazzale Aldo Moro 5, 00185, Rome, Italy

    S. Saccoccio & E. Agostinelli

Authors
  1. V. Battaglia
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  2. S. Grancara
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  3. J. Satriano
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  4. S. Saccoccio
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  5. E. Agostinelli
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  6. A. Toninello
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Correspondence to A. Toninello.

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Battaglia, V., Grancara, S., Satriano, J. et al. Agmatine prevents the Ca2+-dependent induction of permeability transition in rat brain mitochondria. Amino Acids 38, 431–437 (2010). https://doi.org/10.1007/s00726-009-0402-0

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  • DOI: https://doi.org/10.1007/s00726-009-0402-0

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