Horm Metab Res 2003; 35(1): 55-61
DOI: 10.1055/s-2003-38392
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Effects of Thyroid State on H2O2 Production by Rat Heart Mitochondria: Sites of Production with Complex I- and Complex II-Linked Substrates

P.  Venditti1 , A.  Puca1 , S.  Di Meo1
  • 1Dipartimento di Fisiologia Generale ed Ambientale, Università di Napoli, Italy
Further Information

Publication History

Received 8 May 2002

Accepted after revision 3 September 2002

Publication Date:
01 April 2003 (online)

Abstract

This work was designed to determine possible effects of altered thyroid states on rates and sites of H2O2 production by rat heart mitochondria. Rates of O2 consumption and H2O2 release, capacities to remove the peroxide, lipid peroxidation, cytochrome oxidase activities and ubiquinone levels were determined in heart mitochondria from euthyroid, hypothyroid, and hyperthyroid rats. Hypothyroidism decreased, whereas hyperthyroidism increased the rates of O2 consumption and H2O2 release during both state 4 and state 3 respiration with Complex I- or Complex II-linked substrates. The percentage of O2 released as H2O2 was not significantly affected by thyroid state. However, the mitochondrial capacity to remove H2O2 increased in the transition from hypothyroid to hyperthyroid state, which indicates that H2O2 production did not modify in proportion to the rate of O2 consumption. The thyroid-state-linked changes in H2O2 production were well correlated with the levels of hydroperoxides. Rates of H2O2 release in the presence of respiratory inhibitors indicated that changes in the H2O2 production occurred at both sites at which H2O2 was generated in euthyroid state. This result and the observation that ubiquinol levels and cytochrome oxidase activities increase in the transition from hypothyroid to hyperthyroid state suggest that the modifications of H2O2 production are due to a modulation by thyroid hormone of mitochondrial content of autoxidisable electron carriers.

References

  • 1 Sies H. Strategies of antioxidant defense.  Eur J Biochem. 1999;  215 213-219
  • 2 Orzechowski A, Ostaszewski P, Brodnika A, Wilczak J, Jank M, Balasinska B, Grzelkowska K, Ploszaj T, Olczak J, Mrówczynska A. Excess of glucocorticoids impairs whole-body antioxidant status in young rats. Relation to the effect of dexamethasone in soleus muscle and spleen.  Horm Metab Res. 200;  32 174-180
  • 3 Asayama K, Kato K. Oxidative muscular injury and its relevance to hyperthyroidism.  Free Radic Biol Med. 1990;  8 293-303
  • 4 Videla L A. Energy metabolism, thyroid calorigenesis, and oxidative stress: functional and cytotoxic consequences.  Redox Report. 2000;  5 265-275
  • 5 Fernandez V, Videla L A. Influence of hyperthyroidism on superoxide radical and hydrogen peroxide production by rat liver submitochondrial particles.  Free Rad Res Commun. 1993;  18 329-335
  • 6 Venditti P, Balestrieri M, Di Meo S, De Leo T. Effect of thyroid state on lipid peroxidation, antioxidant defences, and susceptibility to oxidative stress in rat tissues.  J Endocrinol. 1997;  155 151-157
  • 7 Venditti P, De Leo T, Di Meo S. Antioxidant-sensitive shortening of ventricular action potential in hyperthyroid rats is independent of lipid peroxidation.  Mol Cell Endocrinol. 1998;  142 15-23
  • 8 Wajdowicz A, Dabros W, Zaczek M. Myocardial damage in thyrotoxicosis: ultrastructural studies.  Pol J Pathol. 1996;  47 127-133
  • 9 Neradilová M, Hrubá F, Nováková V, Bahosová I. Investigations of the relationship between thyroid function and α-tocopherol concentration of serum and in some organs of the rat.  Int J Vit Nutr Res. 1973;  43 283-290
  • 10 Mano T, Sinohara R, Sawai Y, Oda N, Nishida Y, Mokuno T, Kotake M, Hamada M, Masunaga R, Nakai A, Nagasaka A. Effects of thyroid hormone on coenzyme Q and other free radical scavengers in rat heart muscle.  J Endocrinol. 1995;  145 131-136.
  • 11 López-Torres M, Romero M, Barja G. Effect of thyroid hormones on mitochondrial oxygen free radical production and DNA oxidative damage in the rat heart.  Mol Cell Endocrinol. 2000;  168 127-134
  • 12 Gornall A G, Bardawill C J, David M M. Determination of serum proteins by means of the biuret reaction.  J Biol Chem. 1949;  177 751-766
  • 13 Barré H, Bailly L, Rouanet J L. Increased oxidative capacity in skeletal muscles from cold-acclimated ducklings: A comparison with rats.  Comp Biochem Physiol. 1987;  88B 519-522
  • 14 Lang J K, Gohil K, Packer L. Simultaneous determination of tocopherols, ubiquinols, and ubiquinones in blood, plasma, tissue homogenates, and subcellular fractions.  Anal Biochem. 1986;  157 106-116
  • 15 Hyslop P A, Sklar L A. A quantitative fluorimetric assay for the determination of oxidant production by polymorphonuclear leukocytes: its use in the simultaneous fluorimetric assay of cellular activation processes.  Anal Biochem. 1984;  141 280-286
  • 16 Venditti P, Masullo P, Di Meo S. Hemoproteins affects H2O2 removal from rat tissues.  Int J Biochem Cell Biol. 2001;  33 293-301
  • 17 Heat R L, Tappel A L. A new sensitive assay for the measurement of hydroperoxides.  Anal Biochem. 1976;  76 184-191
  • 18 Venditti P, Di Meo S, De Leo T. Effect of thyroid state on characteristics determining the susceptibility to oxidative stress of mitochondrial fractions from rat liver.  Cell Physiol Biochem. 1996;  6 283-295
  • 19 Venditti P, Costagliola I R, Di Meo S. H2O2 production and response to stress conditions by mitochondrial fractions from rat liver.  J Bioenerg Biomembr. 2002;  34 115-125
  • 20 Turrens J F, Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine hear mitochondria.  Biochem J. 1980;  191 421-427
  • 21 Dionisi O, Galeotti T, Terranova T, Azzi A. Superoxide radicals and hydrogen peroxide formation in mitochondria from normal and neoplastic tissues.  Biochim Biophys Acta. 1975;  403 292-300
  • 22 Boveris A, Chance B. The mitochondrial generation of hydrogen peroxide.  Biochem J. 1973;  134 707-716
  • 23 Nishiki K, Ericińska M, Wilson D F, Cooper S. Evaluation of oxidative phosphorylation in hearts from euthyroid, hypothyroid, and hyperthyroid rats.  Am J Physiol. 1978;  235 C212-C219
  • 24 Forman H J, Boveris A. Superoxide radical and hydrogen peroxide in mitochondria. In: Pryor WA (ed) Free radicals in biology. New York; Academic Press 1982: 65-90
  • 25 Loschen G, Flohé L, Chance B. Respiratory chain linked H2O2 production in pigeon heart mitochondria.  FEBS Lett. 1971;  18 261-264
  • 26 Hansford R G, Hogue B A, Mildaziene V. Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age.  J Bioenerg Biomembr. 1997;  29 89-95
  • 27 Konstantinov A A, Ruuge E K. Semiquinone Q in the respiratory chain of electron transport particles: electron spin resonance studies.  FEBS Lett. 1977;  81 137-141
  • 28 Cadenas E, Boveris A. Enhancement of hydrogen peroxide formation by protophores and ionophores in antimycin-supplemented mitochondria.  Biochem J. 1980;  188 31-37
  • 29 Herrero A, Barja G. Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon.  Mech Ageing Dev. 1997;  98 95-111
  • 30 Cannon B, Nedergaard J. The biochemistry of an inefficient tissue: brown adipose tissue.  Essays Biochem. 1985;  20 110-164
  • 31 Teshima Y, Saikawa T, Yonemochi H, Hidaka S, Yoshimatsu H, Sakata T. Alteration of heart uncoupling protein-2 mRNA regulated by sympathetic nerve and triiodothyronine during postnatal period in rats.  Biochim Biophys Acta. 1999;  1448 409-415
  • 32 de Lange P, Lanni A, Beneduce L, Moreno M, Lombardi A, Silvestri E, Goglia F. Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone.  Endocrinology. 2001;  142 3414-3420
  • 33 Négre-Salvayre A, Hirtz C, Carrera G, Cazenave R, Troly M, Salvayre R, Pénicaud L, Casteilla L. A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation.  FASEB J. 1997;  11 809-815
  • 34 Vidal-Puig A J, Grujic D, Zhang C Y, Hagen T, Boss O, Ido Y, Szczepanik A, Wade J, Mootha V, Cortright R, Muoio D M, Lowell B B. Energy metabolism in uncoupling protein-3 gene knockout mice.  J Biol Chem. 2000;  275 16 258-16 266
  • 35 Echtay K S, Winkler E, Frischmuth K, Klingenberg M. Uncoupling proteins-2 and -3 are highly active H+ transporters and highly nucleotide sensitive when activated by coenzyme Q (ubiquinone).  PNAS. 2001;  98 1416-1421

Dr. S. Di Meo

Dipartimento di Fisiologia Generale ed Ambientale · Università di Napoli “Federico II” ·

Via Mezzocannone 8 · 80134 Napoli · Italy ·

Phone: + 39 (81) 552 77236

Fax: + 39 (81) 552 6194 ·

Email: dimeo@biol.dgbm.unina.it

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