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Amino Acids

, Volume 38, Issue 2, pp 431–437 | Cite as

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

  • V. Battaglia
  • S. Grancara
  • J. Satriano
  • S. Saccoccio
  • E. Agostinelli
  • A. Toninello
Original Article

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.

Keywords

Rat brain mitochondria Agmatine Mitochondrial permeability transition Ca2+ Reactive oxygen species 

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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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • V. Battaglia
    • 1
  • S. Grancara
    • 1
  • J. Satriano
    • 2
  • S. Saccoccio
    • 3
    • 4
  • E. Agostinelli
    • 3
    • 4
  • A. Toninello
    • 1
  1. 1.Department of Biological ChemistryUniversity of PaduaPaduaItaly
  2. 2.Division of Nephrology-Hypertension, Department of MedicineThe Veterans Administration San Diego Healthcare System, University of CaliforniaSan DiegoUSA
  3. 3.Department of Biochemical SciencesSAPIENZA, University of RomeRomeItaly
  4. 4.CNR, Biology and Molecular Pathology InstitutesRomeItaly

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