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Mitochondrial oxidative stress induced by Ca2+ and monoamines: different behaviour of liver and brain mitochondria in undergoing permeability transition

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Abstract

Mitochondrial permeability transition (MPT) is correlated with the opening of a nonspecific pore, the so-called transition pore, that triggers bidirectional traffic of inorganic solutes and metabolites across the mitochondrial membrane. This phenomenon is caused by supraphysiological Ca2+ concentrations and by other compounds leading to oxidative stress, while cyclosporin A, ADP, bongkrekic acid, antioxidant agents and naturally occurring polyamines strongly inhibit it. The effects of polyamines, including the diamine agmatine, have been widely studied in several types of mitochondria. The effects of monoamines on MPT have to date, been less well-studied, even if they are involved in a variety of neurological and neuroendocrine processes. This study shows that in rat liver mitochondria (RLM), monoamines such as tyramine, serotonin and dopamine amplify the swelling induced by calcium, and increase the oxidation of thiol groups and the production of hydrogen peroxide, effects that are counteracted by the above-mentioned inhibitors. In rat brain mitochondria (RBM), the monoamines do not amplify calcium-induced swelling, even if they demonstrate increases in the extent of oxidation of thiol groups and hydrogen peroxide production. In these mitochondria, the antioxidants are not at all or scarcely effective in suppressing mitochondrial swelling. In conclusion, we hypothesize that different mechanisms induce the MPT in the two different types of mitochondria evaluated. Calcium and monoamines induce oxidative stress in RLM, which in turn appears to induce and amplify MPT. This process is not apparent in RBM, where MPT seems resistant to oxidative stress.

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Abbreviations

AdNT:

Adenine nucleotide translocase

BHT:

Butyl hydroxy toluene

BKA:

Bongkrekic acid

CsA:

Cyclosporin A

CyP-D:

Cyclophillin D

DA:

Dopamine

DTE:

Dithioerythritol

DTNB:

5,5′-Dithio-bis (2-nitrobenzoic acid)

ΔΨ:

Electrical transmembrane potential

MAO:

Monoamine oxidase

MPT:

Mitochondrial permeability transition

NEM:

N-Ethylmaleimide

PTP:

Permeability transition pore

RBM:

Rat brain mitochondria

RLM:

Rat liver mitochondria

ROS:

Reactive oxygen species

SER:

Serotonin

TPP+ :

Tetraphenylphosphonium

TXT:

Toloxatone

TYR:

Tyramine

References

  • Agostinelli E, Arancia G, Vedova LD, Belli F, Marra M, Salvi M, Toninello A (2004) The biological functions of polyamine oxidation products by amine oxidases: perspectives of clinical applications. Amino Acids 27:347–358

    Article  PubMed  CAS  Google Scholar 

  • Agostinelli E, Marques MP, Calheiros R, Gil FP, Tempera G, Viceconte N, Battaglia V, Grancara S, Toninello A (2010) Polyamines: fundamental characters in chemistry and biology. Amino Acids 38:393–403

    Article  PubMed  CAS  Google Scholar 

  • Arndt MA, Battaglia V, Parisi E, Lortie MJ, Isome M, Baskerville C, Pizzo DP, Ientile R, Colombatto S, Toninello A, Satriano J (2009) The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis. Am J Physiol Cell Physiol 296:C1411–C1419

    Article  PubMed  CAS  Google Scholar 

  • Battaglia V, Rossi CA, Colombatto S, Grillo MA, Toninello A (2007) Different behavior of agmatine in liver mitochondria: inducer of oxidative stress or scavenger of reactive oxygen species? Biochim Biophys Acta 1768:1147–1153

    Article  PubMed  CAS  Google Scholar 

  • Battaglia V, Grancara S, Satriano J, Saccoccio S, Agostinelli E, Toninello A (2010) Agmatine prevents the Ca(2+)-dependent induction of permeability transition in rat brain mitochondria. Amino Acids 38:431–437

    Article  PubMed  CAS  Google Scholar 

  • Bisaglia M, Soriano ME, Arduini I, Mammi S, Bubacco L (2010) Molecular characterization of dopamine-derived quinones reactivity toward NADH and glutathione: implications for mitochondrial dysfunction in Parkinson disease. Biochim Biophys Acta 1802:699–706

    PubMed  CAS  Google Scholar 

  • Boveris A, Martino E, Stoppani AO (1977) Evaluation of the horseradish peroxidase scopoletin method for the measurement of hydrogen peroxide formation in biological systems. Anal Biochem 80:145–158

    Article  PubMed  CAS  Google Scholar 

  • Brenner-Lavie H, Klein E, Zuk R, Gazawi H, Ljubuncic P, Ben-Shachar D (2008) Dopamine modulates mitochondrial function in viable SH-SY5Y cells possibly via its interaction with complex I: relevance to dopamine pathology in schizophrenia. Biochim Biophys Acta 1777:173–185

    Article  PubMed  CAS  Google Scholar 

  • Butterworth RF (2000) Complications of cirrhosis III. Hepatic encephalopathy. J Hepatol 32:171–180

    Article  PubMed  CAS  Google Scholar 

  • Dalla Via L, Salvi M, Di Noto V, Stefanelli C, Toninello A (2004) Membrane binding and transport of N-aminoethyl-1, 2-diamino ethane (dien) and N-aminopropyl-1, 3-diamino propane (propen) by rat liver mitochondria and their effects on membrane permeability transition. Mol Membr Biol 21:109–118

    Article  PubMed  CAS  Google Scholar 

  • Gornall AG, Bardawill CJ, David MM (1949) Determination of serum proteins by means of the biuret method. J Biol Chem 177:751–766

    PubMed  CAS  Google Scholar 

  • Grijalba MT, Vercesi AE, Schreier S (1999) Ca(2+)-induced increased lipid packing and domain formation in submitochondrial particles. A possible early step in the mechanism of Ca(2+)-stimulated generation of reactive oxygen species by the respiratory chain. Biochemistry 38:13279–13287

    Article  PubMed  CAS  Google Scholar 

  • Halestrap AP (2009) What is the mitochondrial permeability transition pore? J Mol Cell Cardiol 46:821–831

    Article  PubMed  CAS  Google Scholar 

  • Halestrap AP, Brenner C (2003) The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Curr Med Chem 10:1507–1525

    Article  PubMed  CAS  Google Scholar 

  • Halestrap AP, Davidson AM (1990) Inhibition of Ca(2+)-induced large-amplitude swelling of liver and heart mitochondria by cyclosporin is probably caused by the inhibitor binding to mitochondrial-matrix peptidyl-prolyl cis-trans isomerase and preventing it interacting with the adenine nucleotide translocase. Biochem J 268:153–160

    PubMed  CAS  Google Scholar 

  • Kamo N, Muratsugu M, Hongoh R, Kobatake Y (1979) Membrane potential of mitochondria measured with an electrode sensitive to tetraphenyl phosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state. J Membr Biol 49:105–121

    Article  PubMed  CAS  Google Scholar 

  • Lapidus RG, Sokolove PM (1994) The mitochondrial permeability transition. Interactions of spermine, ADP, and inorganic phosphate. J Biol Chem 269:18931–18936

    PubMed  CAS  Google Scholar 

  • Leung AWC, Varanyuwatana P, Halestrap AP (2008) The mitochondrial phosphate carrier interacts with cyclophilin D and may play a key role in the permeability transition. J Biol Chem 283:26312–26323

    Article  PubMed  CAS  Google Scholar 

  • Loschen G, Flohe L, Chance B (1971) Respiratory chain linked H(2)O(2) production in pigeon heart mitochondria. FEBS Lett 18:261–264

    Article  PubMed  CAS  Google Scholar 

  • Marcocci L, De Marchi U, Salvi M, Milella ZG, Nocera S, Agostinelli E, Mondovi B, Toninello A (2002) Tyramine and monoamine oxidase inhibitors as modulators of the mitochondrial membrane permeability transition. J Membr Biol 188:23–31

    Article  PubMed  CAS  Google Scholar 

  • Mohanty JG, Jaffe JS, Schulman ES, Raible DG (1997) A highly sensitive fluorescent micro-assay of H2O2 release from activated human leukocytes using a dihydroxyphenoxazine derivative. J Immunol Methods 202:133–141

    Article  PubMed  CAS  Google Scholar 

  • Nicholls DG (1978) Calcium transport and proton electrochemical potential gradient in mitochondria from guinea-pig cerebral cortex and rat heart. Biochem J 170:511–522

    PubMed  CAS  Google Scholar 

  • Nocito A, Dahm F, Jochum W, Jang JH, Georgiev P, Bader M, Renner EL, Clavien PA (2007) Serotonin mediates oxidative stress and mitochondrial toxicity in a murine model of nonalcoholic steatohepatitis. Gastroenterology 133:608–618

    Article  PubMed  CAS  Google Scholar 

  • Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium–apoptosis link. Nat Rev Mol Cell Biol 4:552–565

    Article  PubMed  CAS  Google Scholar 

  • Rajput A, Zesiewicz TA, Hauser RA (2008) Monoamine oxidase inhibitors In: Factor SA and Weiner WJ (eds) Parkinson’s disease. Diagnosis and clinical management. Demos Medical Publishing, New York, pp 499–514

    Google Scholar 

  • Remaury A, Ordener C, Shih J, Parini A (1999) Relationship between I2 imidazoline binding sites and monoamine oxidase B in liver. Ann N Y Acad Sci 881:32–34

    Article  PubMed  CAS  Google Scholar 

  • Richardson JS (1993) On the functions of monoamine oxidase, the emotions, and adaptation to stress. Int J Neurosci 70:75–84

    Article  PubMed  CAS  Google Scholar 

  • Santos AC, Uyemura SA, Lopes JL, Bazon JN, Mingatto FE, Curti C (1998) Effect of naturally occurring flavonoids on lipid peroxidation and membrane permeability transition in mitochondria. Free Radic Biol Med 24:1455–1461

    Article  PubMed  CAS  Google Scholar 

  • Sava IG, Battaglia V, Rossi CA, Salvi M, Toninello A (2006) Free radical scavenging action of the natural polyamine spermine in rat liver mitochondria. Free Radic Biol Med 41:1272–1281

    Article  PubMed  CAS  Google Scholar 

  • Schneider WC, Hogeboon HG (1953) Intracellular distribution of enzymes: XI. Glutamic dehydrogenase. J Biol Chem 204:233–238

    PubMed  Google Scholar 

  • Stevanato R, Cardillo S, Braga M, De Iuliis A, Battaglia V, Toninello A, Agostinelli E, Vianello F (2011) Preliminary kinetic characterization of a copper amine oxidase from rat liver mitochondria matrix. Amino Acids 40:713–720

    Article  PubMed  CAS  Google Scholar 

  • Tassani V, Biban C, Toninello A, Siliprandi D (1995) Inhibition of mitochondrial permeability transition by polyamines and magnesium: importance of the number and distribution of electric charges. Biochem Biophys Res Commun 207:661–667

    Article  PubMed  CAS  Google Scholar 

  • Toninello A, Salvi M, Mondovì B (2004) Interaction of biologically active amines with mitochondria and their role in the mitochondrial-mediated pathway of apoptosis. Curr Med Chem 11:2349–2374

    PubMed  CAS  Google Scholar 

  • Youdim MB, Gross A, Finberg JP (2001) Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol 132:500–506

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Istituto Pasteur-Fondazione Cenci Bolognetti for its financial support.

Conflict of interest

The authors declare that they have not conflict of interest.

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Authors and Affiliations

  1. Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131, Padua, Italy

    Silvia Grancara, Valentina Battaglia, Pamela Martinis, Antonio Toninello & Renzo Deana

  2. Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome and CNR, Institute Biology and Molecular Pathology, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Nikenza Viceconte & Enzo Agostinelli

Authors
  1. Silvia Grancara
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  2. Valentina Battaglia
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  3. Pamela Martinis
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  4. Nikenza Viceconte
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  5. Enzo Agostinelli
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  6. Antonio Toninello
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  7. Renzo Deana
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Correspondence to Antonio Toninello.

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Grancara, S., Battaglia, V., Martinis, P. et al. Mitochondrial oxidative stress induced by Ca2+ and monoamines: different behaviour of liver and brain mitochondria in undergoing permeability transition. Amino Acids 42, 751–759 (2012). https://doi.org/10.1007/s00726-011-0991-2

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  • DOI: https://doi.org/10.1007/s00726-011-0991-2

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