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Increased susceptibility of mitochondria isolated from frontal cortex and hippocampus of vitamin A-treated rats to non-aggregated amyloid-β peptides 1–40 and 1–42

Published online by Cambridge University Press:  24 June 2014

Marcos R. de Oliveira ,
Ricardo F. da Rocha  and
José C. F. Moreira
Marcos R. de Oliveira*
Affiliation:
Centro de Estudos em Estresse Oxidativo (Lab. 32), Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Ricardo F. da Rocha
Affiliation:
Centro de Estudos em Estresse Oxidativo (Lab. 32), Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
José C. F. Moreira
Affiliation:
Centro de Estudos em Estresse Oxidativo (Lab. 32), Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
*
Marcos Roberto de Oliveira, Centro de Estudos em Estresse Oxidativo (Lab. 32), Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. Tel: 555133085577/78; Fax: +55 51 3308 5540; E-mail: mrobioq@yahoo.com.br; mrobioq@gmail.com
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Extract

Objective: Vitamin A is a redox-active molecule and its inadvertent utilisation as a preventive therapy against ageing or neurodegeneration has become a harmful habit among humans at different ages. Mitochondrial dysfunction and redox impairment may be induced by vitamin A supplementation experimentally. Nonetheless, it is still not clear by which mechanisms vitamin A elicits such effects. Then, we performed this investigation to analyse whether mitochondria isolated from frontal cortex and hippocampus of vitamin A-treated rats are more sensitive to a challenge with amyloid-β (Aβ) peptides 1–40 or 1–42.

Methods: Adult Wistar rats received vitamin A at 1000–9000 IU/kg/day orally for 28 days. Then, mitochondria were isolated and the challenge with Aβ peptides 1–40 or 1–42 (at 0.2 or 0.1 μM, respectively) for 10 min was carried out before mitochondrial electron transfer chain enzyme activity, superoxide anion radical (O2−•) production and 3-nitrotyrosine content quantification.

Results: Mitochondria obtained from vitamin A-treated rats are more sensitive to Aβ peptides 1–40 or 1–42 than mitochondria isolated from the control group, as decreased mitochondrial complex enzyme activity and increased O2−• production and 3-nitrotyrosine content were observed in incubated mitochondria isolated from vitamin A-treated rats.

Conclusion: These data suggest that oral intake of vitamin A at clinical doses increases the susceptibility of mitochondria to a neurotoxic agent even at low concentrations.

Keywords

amyloid-β peptidemitochondrial dysfunction3-nitrotyrosinevitamin A
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 2 , April 2012 , pp. 101 - 108
Copyright
Copyright © Cambridge University Press 2011

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References

1.Lane, MA, Bailey, SJ.Role of retinoids signaling in the adult brain. Prog Neurobiol 2005;75:275–293.CrossRefGoogle ScholarPubMed
2.Snodgrass, SR.Vitamin neurotoxicity. Mol Neurobiol 1992;6:41–73.Google ScholarPubMed
3.De Oliveira, MR, Moreira, JCF.Acute and chronic vitamin A supplementation at therapeutic doses induces oxidative stress to submitochondrial particles isolated from cerebral cortex and cerebellum of adult rats. Toxicol Lett 2007;173:145–150.CrossRefGoogle ScholarPubMed
4.De Oliveira, MR, Silvestrin, RB, Mello e Souza, T, Moreira, JCF.Oxidative stress in the hippocampus, anxiety-like behavior and decreased locomotory and exploratory activity of adult rats: effects of sub acute vitamin A supplementation at therapeutic doses. Neurotoxicology 2007;28:1191–1199.CrossRefGoogle ScholarPubMed
5.De Oliveira, MR, Pasquali, MAB, Silvestrin, RB, Mello e Souza, T, Moreira, JCF.Vitamin A supplementation induces a prooxidative state in the striatum and impairs locomotory and exploratory activity of adult rats. Brain Res 2007;1169:112–119.CrossRefGoogle Scholar
6.De Oliveira, MR, Moreira, JCF.Impaired redox state and respiratory chain enzyme activities in the cerebellum of vitamin A-treated rats. Toxicology 2008;253:125–130.CrossRefGoogle ScholarPubMed
7.De Oliveira, MR, Silvestrin, RB, Mello, E, Souza, T, Moreira, JCF.Therapeutic vitamin A doses increase the levels of markers of oxidative insult in substantia nigra and decrease locomotory and exploratory activity in rats after acute and chronic supplementation. Neurochem Res 2008;33:378–383.CrossRefGoogle ScholarPubMed
8.De Oliveira, MR, Oliveira, MWS, Behr, GA, Hoff, MLM, Da Rocha, RF, Moreira, JCF.Evaluation of the effects of vitamin A supplementation on adult rat substantia nigra and striatum redox and bioenergetics states: mitochondrial impairment, increased 3-nitrotyrosine and α-synuclein, but decreased D2 receptor contents. Progr Neuropsychopharmacol Biol Psychiatry 2009;33:353–362.CrossRefGoogle ScholarPubMed
9.De Oliveira, MR, Oliveira, MWS, Da Rocha, RF, Moreira, JCF.Vitamin A supplementation at pharmacological doses induces nitrosative stress on the hypothalamus of adult Wistar rats. Chem Biol Interact 2009;180:407–413.CrossRefGoogle ScholarPubMed
10.De Oliveira, MR, Oliveira, MWS, Behr, GA, Moreira, JCF.Vitamin A supplementation at clinical doses induces a dysfunction in the redox and bioenergetics states, but did not change neither caspases activities nor TNF-alpha levels in the frontal cortex of adult Wistar rats. J Psychiatr Res 2009;43:754–762.CrossRefGoogle Scholar
11.Bjelakovic, G, Nikolova, D, Gluud, LL, Simonetti, RG, Gluud, C.Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systemic review and meta-analysis. J Am Med Assoc 2007;297:842–857.CrossRefGoogle Scholar
12.Omenn, GS, Goodman, G, Thornquist, M et al. The beta-carotene and retinol efficacy trail (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers. Cancer Res 1994;54:2038s–2043s.Google Scholar
13.Omenn, GS, Goodman, GE, Thornquist, MD et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334:1150–1155.CrossRefGoogle ScholarPubMed
14.Tsunati, H, Iwasaki, H, Kawai, Y, Tanaka, T, Ueda, T, Uchida, M, Nakamura, T.Reduction of leukemia cell growth in a patient with acute promyelocytic leukemia treated by retinol palmitate. Leukemia Res 1990;14:595–600.Google Scholar
15.Tsunati H, UEDAT, Uchid, AM, Nakamura, T.Pharmacological studies of retinol palmitate and its clinical effect in patients with acute non-lymphocytic leukemia. Leukemia Res 1991;15:463–471.Google Scholar
16.Allen, LH, Haskell, M.Estimating the potential for vitamin A toxicity in women and young children. J Nutr 2002;132:2907S–2919S.CrossRefGoogle ScholarPubMed
17.Myhre, AM, Carlsen, MH, Bohn, SK, Wold, HL, Laake, P, Blomhoff, R.Water-miscible emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations. Am J Clin Nutr 2003;78:1152–1159.CrossRefGoogle ScholarPubMed
18.Mactier, H, Weaver, LT.Vitamin A and preterm infants: what we know, what we don't know, and what we need to know. Arch Dis Child Fetal Neonatal Ed 2005;90:103–108.CrossRefGoogle ScholarPubMed
19.Jick, SS, Kremers, HM, Vasilakis-Scaramozza, C.Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol 2000;136:1231–1236.CrossRefGoogle ScholarPubMed
20.Halliweel, B.Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006;97:1634–1658.CrossRefGoogle Scholar
21.Klamt, F, De Oliveira, MR, Moreira, JCF.Retinol induces permeability transition and cytochrome c release from rat liver mitochondria. Biochim Biophys Acta 2005;1726:14–20.CrossRefGoogle ScholarPubMed
22.Shapira, AH, Mann, VM, Cooper, JM et al. Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson's disease. J Neurochem 1990;55:2142–2145.CrossRefGoogle Scholar
23.Fisher, JC, Ruitenbeek, W, Berden, JÁ et al. Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 1985;153:23–36.CrossRefGoogle Scholar
24.Rustin, P, Chretien, D, Bourgeron, T, Gérard, B, Rötig, A, Saudubray, JM, Munnich, A.Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 1994;228:35–51.CrossRefGoogle ScholarPubMed
25.Poderoso, JJ, Carreras, MC, Lisdero, C, Riobo, N, Schopfer, F, Boveris, A.Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 1996;328:85–92.CrossRefGoogle ScholarPubMed
26.Ferri, CP, Prince, M, Brayne, C et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112–2117.CrossRefGoogle ScholarPubMed
27.Kalaria, RN, Maestre, GE, Arizaga, R et al. Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol 2008;7:812–826.CrossRefGoogle ScholarPubMed
28.Hawton, K, Van Heeringen, K.Suicide. Lancet 2009;373:1372–1381.CrossRefGoogle ScholarPubMed
29.Bremner, JD, Fani, N, Ashraf, A et al. Functional brain imaging alterations in acne patients treated with isotretinoin. Am J Psychiatr 2005;162:983–991.CrossRefGoogle ScholarPubMed
30.O'Reilly, K, Bailey, SJ, Lane, MA.Retinoid-mediated regulation of mood: possible cellular mechanisms. Exp Biol Med 2008;233:251–258.CrossRefGoogle ScholarPubMed
31.Berg, D, Youdim, MBH, Riederer, P.Redox imbalance. Cell Tissue Res 2004;318:201–213.CrossRefGoogle ScholarPubMed
32.Manczak, M, Anekonda, TS, Henson, E, Park, BS, Quinn, P, Reddy, H.Mitochondria are a direct site of Aβ accumulation in Alzheimer's disease neurons: implications for frre radical generation and oxidative damage in disease progression. Hum Mol Genet 2006;15:1437–1449.CrossRefGoogle Scholar
33.Chen, X, Yan, SD.Mitochondrial Aβ: a potential cause of metabolic dysfunction in Alzheimer's disease. IUBMB Life 2006;58:686–694.CrossRefGoogle ScholarPubMed
34.Pavlov, PF, Petersen, CH, Glaser, E, Ankarcrona, M.Mitochondrial accumulation of APP and Aβ: significance for Alzheimer's disease pathogenesis. J Cell Mol Med 2009;13:4137–4145.CrossRefGoogle Scholar
35.Du, H, Guo, L, Fang, F et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med 2008;14:1097–1105.CrossRefGoogle ScholarPubMed
36.Yao, J, Irwin, RW, Zhao, L, Nilsen, J, Hamilton, RT, Brinton, RD.Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 2009;106:14670–14675.CrossRefGoogle ScholarPubMed