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Effects of vitamin A deficiency on mitochondrial function in rat liver and heart

Published online by Cambridge University Press:  09 March 2007

Ernesto Estornell ,
José R. Tormo ,
Pilar Marín ,
Jaime Renau-Piqueras ,
Joaquín Timoneda  and
Teresa Barber
Ernesto Estornell
Affiliation:
Department de Bioquímica Biologia Molecular, Facultat de Farmàcia, Universitat de València, Spain
José R. Tormo
Affiliation:
Department de Bioquímica Biologia Molecular, Facultat de Farmàcia, Universitat de València, Spain
Pilar Marín
Affiliation:
Department de Bioquímica Biologia Molecular, Facultat de Farmàcia, Universitat de València, Spain
Jaime Renau-Piqueras
Affiliation:
Centro de Investigación, Hospital La Fé, València, Spain
Joaquín Timoneda
Affiliation:
Department de Bioquímica Biologia Molecular, Facultat de Farmàcia, Universitat de València, Spain
Teresa Barber*
Affiliation:
Department de Bioquímica Biologia Molecular, Facultat de Farmàcia, Universitat de València, Spain
*
*Corresponding author: Teresa Barber, fax +34 6 3864917 email barber@uv.es
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Abstract

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The aim of this study was to investigate comparative effects of vitamin A deficiency on respiratory activity and structural integrity in liver and heart mitochondria. Male rats were fed a liquid control diet (control rats) or a liquid vitamin A-deficient diet (vitamin A-deficient rats) for 50 days. One group of vitamin-A deficient rats was refed a control diet for 15 days (vitamin A-recovered rats). To assess the respiratory function of mitochondria the contents of coenzyme Q (ubiquinone, CoQ), cytochrome c and the activities of the whole electron transport chain and of each of its respiratory complexes were evaluated. Chronic vitamin A deficiency promoted a significant increase in the endogenous coenzyme Q content in liver and heart mitochondria when compared with control values. Vitamin A deficiency induced a decrease in the activity of complex I (NADH–CoQ reductase) and complex II (succinate–CoQ reductase) and in the levels of complex I and cytochrome c in heart mitochondria. However, NADH and succinate oxidation rates were maintained at the control levels due to an increase in the CoQ content in accordance with the kinetic behaviour of CoQ as an homogeneous pool. On the contrary, the high CoQ content did not affect the electron-transfer rate in liver mitochondria, whose integrity was preserved from the deleterious effects of the vitamin A deficiency. Ultrastuctural assessment of liver and heart showed that vitamin A deficiency did not induce appreciable alterations in the morphology of their mitochondria. After refeeding the control diet, serum retinol, liver and heart CoQ content and the activity of complex I and complex II in heart mitochondria returned to normality. However, the activities of both whole electron transfer chain and complex I in liver were increased over the control values. The interrelationships between physiological antioxidants in biological membranes and the beneficial effects of their administration in mitochondrial diseases are discussed.

Keywords

Vitamin A deficiencyCoenzyme Q (ubiquinone)Mitochondrial respiratory chain
Type
Research Article
Information
British Journal of Nutrition , Volume 84 , Issue 6 , December 2000 , pp. 927 - 934
Copyright
Copyright © The Nutrition Society 2000

References

Akmal, KM, Dufour, JM, Vo, M, Higginson, S & Kim, KH (1998) Ligand dependent regulation of retinoic acid receptor alpha in rat testis:. in vivo response to depletion and repletion of vitamin A. Endocrinology 139, 1239–1248.CrossRefGoogle ScholarPubMed
Barber, T, Triguero, A, Martínez-López, I, Torres, L, García, C, Miralles, VJ & Viña, JR (1999) Elevated expression of liver gamma-cystathionase is required for the maintenance of lactation in rats. Journal of Nutrition 129, 928–933.CrossRefGoogle ScholarPubMed
Barua, AB & Olson, JA (1998) Reversed-phase gradient high-performance liquid chromatographic procedure for simultaneous analysis of very polar to nonpolar retinoids, carotenoids and tocopherols in animals and plant samples. Journal of Chromatography B 707, 69–79.CrossRefGoogle ScholarPubMed
Burton (1994) Vitamin E: molecular and biological function. Proceedings of the Nutrition Society 53, 251–262.CrossRefGoogle Scholar
Ciaccio, M, Valenza, M, Tesoriere, L, Bongiorno, A, Albiero, R & Livrea, L (1993) Vitamin A inhibits doxorubicin-induced membrane lipid peroxidation in rat tissues. in vivo. Archives of Biochemistry and Biophysics 302, 103–108.Google Scholar
Cooper, JM, Petty, RKH, Hayes, DJ, Morgan-Hughes, JA & Clark, JB (1988) Chronic administration of the oral hypoglycaemic agent diphenyleneiodonium to rats. An animal model of impaired oxidative phosphorylation (mitochondrial myopathy). Biochemical Pharmacology 37, 687–694.CrossRefGoogle ScholarPubMed
Degli Esposti, M & Lenaz, G (1982) Kinetics of ubiquinol-1-cytochrome c reductase in bovine heart mitochondria and submitochondrial particles. Biochimica et Biophysica Acta 682, 189–200.CrossRefGoogle ScholarPubMed
Estornell, E, Fato, R, Castelluccio, C, Cavazzoni, M, Parenti Castelli, G & Lenaz, G (1992) Saturation kinetics of coenzyme Q in NADH and succinate oxidation in beef heart mitochondria. FEBS Letters 311, 107–109.CrossRefGoogle ScholarPubMed
Estornell, E, Fato, R, Pallotti, F & Lenaz, G (1993) Assay conditions for the mitochondrial NADH:coenzyme Q oxidoreductase. FEBS Letters 332, 127–131.CrossRefGoogle ScholarPubMed
Estornell, E, Barber, T & Cabo, J (1994) Improved nitrogen metabolism in rats fed on lipid-rich liquid diets. British Journal of Nutrition 71, 361–373.CrossRefGoogle ScholarPubMed
Estornell, E, Tormo, JR & Barber, T (1997) A deficiency in respiratory complex I in heart mitochondria from vitamin A-deficient rats is counteracted by an increase in coenzyme Q. Biochemical and Biophysical Research Communications 233, 451–454.CrossRefGoogle ScholarPubMed
Evarts, RP, Hu, Z, Omori, N, Omori, M, Marsden, ER & Thogeirsson, SS (1995) Effect of vitamin A deficiency on the integrity of hepatocytes after partial hepatectomy. American Journal of Pathology 147, 699–706.Google ScholarPubMed
Genova, ML, Castelluccio, C, Fato, R, Parenti Castelli, G, Merlo Pich, M, Formiggini, G, Bovina, C, Marchetti, M & Lenaz, G (1995) Major changes in complex I activity in mitochondria from aged rats may not be detected by direct assay of NADH:coenzyme Q reductase. Biochemical Journal 311, 105–109.Google Scholar
Green, DR & Reed, JC (1998) Mitochondria and apoptosis. Science 281, 1309–1312.Google Scholar
Johnson, D & Lardy, H (1967) Isolation of liver or kidney mitochondria. Methods in Enzymology 10, 94–96.CrossRefGoogle Scholar
Krahenbuhl, S & Reichen, J (1992) Adaptation of mitochondrial metabolism in liver cirrhosis. Different strategies to maintain a vital function. Scandinavian Journal of Gastroenterology 193, 90–96.CrossRefGoogle ScholarPubMed
Kröger, A (1978) Determination of contents and redox states of ubiquinone and menaquinone. Methods in Enzymology 53, 579–591.CrossRefGoogle ScholarPubMed
Lea, RG, Riley, SC, Antipatis, C, Hannah, L, Ashworth, CJ, Clark, DA & Critchley, HO (1999) Cytokines and the regulation of apoptosis in reproductive tissues: a review. American Journal of Reproductive Immunology 42, 100–109.Google Scholar
Lenaz, G, Fato, R, Genova, ML, Formiggini, G, Parenti Castelli, G & Bovina, C (1995) Underevaluation of complex I activity by the direct assay of NADH–coenzyme Q reductase in rat liver mitochondria. FEBS Letters 366, 119–121.Google Scholar
Lenaz, G, Bovina, C, Castelluccio, C, Cavazzoni, M, Estornell, E, Fato, R, Huertas, JR, Merlo-Pich, M, Pallotti, F, Parenti Castelli, G & Rauchova, H (1995) Modes of coenzyme Q function in electron transfer. Protoplasma 184, 50–62.CrossRefGoogle Scholar
Leo, MA, Sato, M & Lieber, CS (1983) Effect of hepatic vitamin A depletion on the liver in humans and rats. Gastroenterology 84, 562–572.Google Scholar
Liu, X, Kim, CN, Yang, J, Jemmerson, R & Wang, X (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147–157.CrossRefGoogle ScholarPubMed
Livrea, MA & Tesoriere, L (1998) Antioxidant activity of vitamin A within lipid environments. In Subcellular Biochemistry, pp. 113–143 [Quinn, PJ and Kagan, VE, editors]. New York: Plenum Press.Google Scholar
Maden, M, Gale, E & Zile, M (1998) The role of vitamin A in the development of the central nervous system. Journal of Nutrition 128, 471S–475S.CrossRefGoogle ScholarPubMed
Morimoto, T, Jikkoh, A, Yokoo, N, Taki, Y, Tanaka, J, Kamiyama, Y, Ozawa, K & Tobe, T (1985) Changes in coenzyme Q level in mitochondria of cirrhotic rat liver. Life Sciences 36, 1577–1580.CrossRefGoogle ScholarPubMed
Morre, DM, Morre, DJ & Walter, M (1981) Vitamin A effects on hepatic Golgi apparatus architecture. European Journal of Cellular Biology 25, 28–35.Google Scholar
Nicholls, P (1976) Catalytic activity of cytochromes c and c 1 in mitochondria and submitochondrial particles. Biochimica et Biophysica Acta 430, 30–45.CrossRefGoogle ScholarPubMed
Packer, L & Landvik, S (1990) Vitamin E in biological systems. Advances in Experimental Medicine and Biology 264, 93–103.Google Scholar
Palace, VP, Khaper, N, Qin, Q & Singal, PK (1999) Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease. Free Radical Biology and Medicine 26, 746–761.CrossRefGoogle ScholarPubMed
Pasatiempo, AM, Taylor, CE & Ross, AC (1991) Vitamin A status and the immune response to pneumococcal polysaccharide: effects of age and early stages of retinol deficiency in rats. Journal of Nutrition 121, 556–562.Google Scholar
Reeves, PG, Nielsen, FH & Fahey, GC (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing Committee on the reformulation of the AIN-76 rodent diet. Journal of Nutrition 123, 1939–1953.Google Scholar
Ross, AC (1992) Vitamin A status: relationship to immunity and the antibody response. Proceedings of the Society for Experimental Biology and Medicine 200, 303–320.CrossRefGoogle ScholarPubMed
Sancho-Tello, M, Renau-Piqueras, J, Báguena-Cervellera, R & Guerri, C (1987) A biochemical and stereological study of neonatal rat hepatocyte subpopulations. Effect of pre- and postnatal exposure to ethanol. Virchows Archives of Biology and Cellular Pathology 54, 170–181.CrossRefGoogle Scholar
Schapira, AHV (1998) Human complex I defects in neurodegenerative diseases. Biochimica et Biophysica Acta 1364, 261–270.CrossRefGoogle ScholarPubMed
Selvaraj, RJ & Susheela, TP (1970) Estimation of serum vitamin A by a microfluorometric procedure. Clinica Chimica Acta 27, 165–170.Google Scholar
Semba, RD (1994) Vitamin A, immunity, and infection. Clinical Infectious Diseases 19, 489–499.Google Scholar
Semba, RD (1999) Vitamin A and immunity to viral, bacterial and protozoan infections. Proceedings of the Nutrition Society 58, 719–727.Google Scholar
Shi, H, Noguchi, N & Niki, E (1999) Comparative study on dynamics of antioxidative action of alpha-tocopherol hydroquinone, ubiquinol and alpha-tocopherol against lipid peroxidation. Free Radical Biology and Medicine 27, 334–346.Google Scholar
Smith, AL (1967) Preparation, properties and conditions for assay of mitochondria: slaughterhouse material, small scale. Methods in Enzymology 10, 81–86.CrossRefGoogle Scholar
Tesoriere, L, Ciaccio, M, Bongiorno, A, Riccio, A, Pintaudi, AM & Livrea, MA (1993) Antioxidant activity of all-trans-retinol in homogeneous solution and in phosphatidylcholine liposomes. Archives of Biochemistry and Biophysics 307, 217–223.Google Scholar
Thomas, PK, Cooper, JM, King, RH, Workman, JM, Schapira, AHV, Goss-Sampson, MA & Muller, DPR (1993) Myopathy in vitamin E deficient rats: muscle fibre necrosis associated with disturbances of mitochondrial function. Journal of Anatomy 183, 451–461.Google ScholarPubMed
Traber, MG & Packer, L (1995) Vitamin E: beyond antioxidant function. American Journal of Clinical Nutrition 62, 1501S–1509S.CrossRefGoogle ScholarPubMed
Vanneste, VH (1966) Molecular proportion of the fixed cytochrome components of the respiratory chain of Keilin–Hartree particles and beef heart mitochondria. Biochimica et Biophysica Acta 113, 175–178.Google Scholar
Wallace, DC (1999) Mitochondrial diseases in man and mouse. Science 283, 1482–1488.Google Scholar
Zile, M (1998) Vitamin A and embryonic development: an overview. Journal of Nutrition 128, 455S–458S.CrossRefGoogle ScholarPubMed