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The Cerebellum
Erschienen in: The Cerebellum 6/2014

01.12.2014 | Original Paper

Pristanic Acid Provokes Lipid, Protein, and DNA Oxidative Damage and Reduces the Antioxidant Defenses in Cerebellum of Young Rats

verfasst von: Estela Natacha Brandt Busanello, Vannessa Gonçalves Araujo Lobato, Ângela Zanatta, Clarissa Günther Borges, Anelise Miotti Tonin, Carolina Maso Viegas, Vanusa Manfredini, César Augusto João Ribeiro, Carmen Regla Vargas, Diogo Onofre Gomes de Souza, Moacir Wajner

Erschienen in: The Cerebellum | Ausgabe 6/2014

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Abstract

Zellweger syndrome (ZS) and some peroxisomal diseases are severe inherited disorders mainly characterized by neurological symptoms and cerebellum abnormalities, whose pathogenesis is poorly understood. Biochemically, these diseases are mainly characterized by accumulation of pristanic acid (Prist) and other fatty acids in the brain and other tissues. In this work, we evaluated the in vitro influence of Prist on redox homeostasis by measuring lipid, protein, and DNA damage, as well as the antioxidant defenses and the activities of aconitase and α-ketoglutarate dehydrogenase in cerebellum of 30-day-old rats. The effect of Prist on DNA damage was also evaluated in blood of these animals. Some parameters were also evaluated in cerebellum from neonatal rats and in cerebellum neuronal cultures. Prist significantly increased malondialdehyde (MDA) levels and carbonyl formation and reduced sulfhydryl content and glutathione (GSH) concentrations in cerebellum of young rats. It also caused DNA strand damage in cerebellum and induced a high micronuclei frequency in blood. On the other hand, this fatty acid significantly reduced α-ketoglutarate dehydrogenase and aconitase activities in rat cerebellum. We also verified that Prist-induced increase of MDA levels was totally prevented by melatonin and attenuated by α-tocopherol but not by the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester, indicating the involvement of reactive oxygen species in this effect. Cerebellum from neonate rats also showed marked alterations of redox homeostasis, including an increase of MDA levels and a decrease of sulfhydryl content and GSH concentrations elicited by Prist. Finally, Prist provoked an increase of dichlorofluorescein (DCFH) oxidation in cerebellum-cultivated neurons. Our present data indicate that Prist compromises redox homeostasis in rat cerebellum and blood and inhibits critical enzymes of the citric acid cycle that are susceptible to free radical attack. The present findings may contribute to clarify the pathogenesis of the cerebellar alterations observed in patients affected by ZS and some peroxisomal disorders in which Prist is accumulated.
Literatur
1.
Ferdinandusse S, Finckh B, de Hingh Y, Stroomer L, Denis S, Kohlschütter A, et al. Evidence for increased oxidative stress in peroxisomal D-bifunctional protein deficiency. Mol Genet Metab. 2003;79(4):281–7.PubMedCrossRef
2.
Ferdinandusse S, Denis S, Clayton P, Graham A, Rees J, Allen J, et al. Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. Nat Genet. 2000;24(2):188–91.PubMedCrossRef
3.
Steinberg S, Chen L, Wei L, Moser A, Moser H, Cutting G, et al. The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. Mol Genet Metab. 2004;83(3):252–63.PubMedCrossRef
4.
Verhoeven N, Jakobs C. Human metabolism of phytanic acid and pristanic acid. Prog Lipid Res. 2001;40(6):453–66.PubMedCrossRef
5.
Scriver C, Beaudet A, Sly W, Valle D. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001.
6.
Ferdinandusse S, Rusch H, van Lint A, Dacremont G, Wanders R, Vreken P. Stereochemistry of the peroxisomal branched-chain fatty acid alpha- and beta-oxidation systems in patients suffering from different peroxisomal disorders. J Lipid Res. 2002;43(3):438–44.PubMed
7.
Fedick A, Jalas C, Treff N. A deleterious mutation in the PEX2 gene causes Zellweger syndrome in individuals of Ashkenazi Jewish descent. Clin Genet. 2013.
8.
Weller S, Rosewich H, Gärtner J. Cerebral MRI as a valuable diagnostic tool in Zellweger spectrum patients. J Inherit Metab Dis. 2008;31(2):270–80.PubMedCrossRef
9.
10.
Rafique M, Zia S, Rana MN, Mostafa OA. Zellweger syndrome—a lethal peroxisome biogenesis disorder. J Pediatr Endocrinol Metab. 2013;26(3–4):377–9.PubMed
11.
Rönicke S, Kruska N, Kahlert S, Reiser G. The influence of the branched-chain fatty acids pristanic acid and Refsum disease-associated phytanic acid on mitochondrial functions and calcium regulation of hippocampal neurons, astrocytes, and oligodendrocytes. Neurobiol Dis. 2009;36(2):401–10.PubMedCrossRef
12.
Busanello EN, Viegas CM, Tonin AM, Grings M, Moura AP, de Oliveira AB, et al. Neurochemical evidence that pristanic acid impairs energy production and inhibits synaptic Na(+), K (+)-ATPase activity in brain of young rats. Neurochem Res. 2011.
13.
Busanello EN, Amaral AU, Tonin AM, Grings M, Moura AP, Eichler P, et al. Experimental evidence that pristanic acid disrupts mitochondrial homeostasis in brain of young rats. J Neurosci Res. 2012;90(3):597–605.PubMedCrossRef
14.
Leipnitz G, Amaral AU, Fernandes CG, Seminotti B, Zanatta A, Knebel LA, et al. Pristanic acid promotes oxidative stress in brain cortex of young rats: a possible pathophysiological mechanism for brain damage in peroxisomal disorders. Brain Res. 2011;1382:259–65.PubMedCrossRef
15.
Evelson P, Travacio M, Repetto M, Escobar J, Llesuy S, Lissi EA. Evaluation of total reactive antioxidant potential (TRAP) of tissue homogenates and their cytosols. Arch Biochem Biophys. 2001;388(2):261–6.PubMedCrossRef
16.
Knebel LA, Zanatta A, Tonin AM, Grings M, Alvorcem Led M, Wajner M, et al. 2-Methylbutyrylglycine induces lipid oxidative damage and decreases the antioxidant defenses in rat brain. Brain Res. 2012;1478:74–82.PubMedCrossRef
17.
Ribas GS, Manfredini V, de Marco MG, Vieira RB, Wayhs CY, Vanzin CS, et al. Prevention by L-carnitine of DNA damage induced by propionic and L-methylmalonic acids in human peripheral leukocytes in vitro. Mutat Res. 2010;702(1):123–8.PubMedCrossRef
18.
Rosenthal R, Hamud F, Fiskum G, Varghese P, Sharpe S. Cerebral ischemia and reperfusion: prevention of brain mitochondrial injury by lidoflazine. J Cereb Blood Flow Metab. 1987;7(6):752–8.PubMedCrossRef
19.
Facci L, Skaper SD. Culture of rat cerebellar granule neurons and application to identify neuroprotective agents. Methods Mol Biol. 2012;846:23–37.PubMedCrossRef
20.
Yagi K. Simple procedure for specific assay of lipid hydroperoxides in serum or plasma. Methods Mol Biol. 1998;108:107–10.PubMed
21.
Leipnitz G, Seminotti B, Haubrich J, Dalcin MB, Dalcin KB, Solano A, et al. Evidence that 3-hydroxy-3-methylglutaric acid promotes lipid and protein oxidative damage and reduces the nonenzymatic antioxidant defenses in rat cerebral cortex. J Neurosci Res. 2008;86(3):683–93.PubMedCrossRef
22.
Schuck PF, Ceolato PC, Ferreira GC, Tonin A, Leipnitz G, Dutra-Filho CS, et al. Oxidative stress induction by cis-4-decenoic acid: relevance for MCAD deficiency. Free Radic Res. 2007;41(11):1261–72.PubMedCrossRef
23.
Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol. 1994;233:357–63.PubMedCrossRef
24.
Aksenov MY, Markesbery WR. Changes in thiol content and expression of glutathione redox system genes in the hippocampus and cerebellum in Alzheimer's disease. Neurosci Lett. 2001;302(2–3):141–5.PubMedCrossRef
25.
26.
Lai J, Cooper A. Brain alpha-ketoglutarate dehydrogenase complex: kinetic properties, regional distribution, and effects of inhibitors. J Neurochem. 1986;47(5):1376–86.PubMedCrossRef
27.
Tretter L, Adam-Vizi V. Generation of reactive oxygen species in the reaction catalyzed by alpha-ketoglutarate dehydrogenase. J Neurosci. 2004;24(36):7771–8.PubMedCrossRef
28.
Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175(1):184–91.PubMedCrossRef
29.
Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, et al. Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen. 2000;35(3):206–21.PubMedCrossRef
30.
Hartmann A, Agurell E, Beevers C, Brendler-Schwaab S, Burlinson B, Clay P, et al. Recommendations for conducting the in vivo alkaline Comet assay. 4th International Comet Assay Workshop. Mutagenesis. 2003;18(1):45–51.PubMedCrossRef
31.
Nadin SB, Vargas-Roig LM, Ciocca DR. A silver staining method for single-cell gel assay. J Histochem Cytochem. 2001;49(9):1183–6.PubMedCrossRef
32.
33.
Browne RW, Armstrong D. Reduced glutathione and glutathione disulfide. Methods Mol Biol. 1998;108:347–52.PubMed
34.
Quincozes-Santos A, Bobermin LD, Souza DG, Bellaver B, Gonçalves CA, Souza DO. Guanosine protects C6 astroglial cells against azide-induced oxidative damage: a putative role of heme oxygenase 1. J Neurochem. 2014;130(1):61–74.PubMedCrossRef
35.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265–75.PubMed
36.
Styskal J, Van Remmen H, Richardson A, Salmon AB. Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models? Free Radic Biol Med. 2012;52(1):46–58.PubMedCentralPubMedCrossRef
37.
Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta. 2003;329(1–2):23–38.PubMedCrossRef
38.
Levine RL. Carbonyl modified proteins in cellular regulation, aging, and disease. Free Radic Biol Med. 2002;32(9):790–6.PubMedCrossRef
39.
Liang LP, Ho YS, Patel M. Mitochondrial superoxide production in kainate-induced hippocampal damage. Neuroscience. 2000;101(3):563–70.PubMedCrossRef
40.
Tretter L, Liktor B, Adam-Vizi V. Dual effect of pyruvate in isolated nerve terminals: generation of reactive oxygen species and protection of aconitase. Neurochem Res. 2005;30(10):1331–8.PubMedCrossRef
41.
42.
Gardner PR, Raineri I, Epstein LB, White CW. Superoxide radical and iron modulate aconitase activity in mammalian cells. J Biol Chem. 1995;270(22):13399–405.PubMedCrossRef
43.
44.
Reiter RJ, Guerrero JM, Escames G, Pappolla MA, Acuña-Castroviejo D. Prophylactic actions of melatonin in oxidative neurotoxicity. Ann N Y Acad Sci. 1997;825:70–8.PubMedCrossRef
45.
Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem. 2006;97(6):1634–58.PubMedCrossRef
46.
Speit G, Hartmann A. The contribution of excision repair to the DNA effects seen in the alkaline single cell gel test (comet assay). Mutagenesis. 1995;10(6):555–9.PubMedCrossRef
47.
D'Errico M, Parlanti E, Dogliotti E. Mechanism of oxidative DNA damage repair and relevance to human pathology. Mutat Res. 2008;659(1–2):4–14.PubMedCrossRef
48.
Altieri F, Grillo C, Maceroni M, Chichiarelli S. DNA damage and repair: from molecular mechanisms to health implications. Antioxid Redox Signal. 2008;10(5):891–937.PubMedCrossRef
49.
Markesbery WR, Lovell MA. DNA oxidation in Alzheimer's disease. Antioxid Redox Signal. 2006;8(11–12):2039–45.PubMedCrossRef
50.
Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S. The HUman MicroNucleus Project—an international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res. 1999;428(1–2):271–83.PubMedCrossRef
51.
52.
Fenech M. In vitro micronucleus technique to predict chemosensitivity. Methods Mol Med. 2005;111:3–32.PubMed
53.
Bergamini CM, Gambetti S, Dondi A, Cervellati C. Oxygen, reactive oxygen species and tissue damage. Curr Pharm Des. 2004;10(14):1611–26.PubMedCrossRef
54.
Lee HC, Wei YH. Oxidative stress, mitochondrial DNA mutation, and apoptosis in aging. Exp Biol Med (Maywood). 2007;232(5):592–606.
55.
56.
Hansen RE, Winther JR. An introduction to methods for analyzing thiols and disulfides: reactions, reagents, and practical considerations. Anal Biochem. 2009;394(2):147–58.PubMedCrossRef
57.
Thomas SR, Neuzil J, Mohr D, Stocker R. Coantioxidants make alpha-tocopherol an efficient antioxidant for low-density lipoprotein. Am J Clin Nutr. 1995;62(6 Suppl):1357S–64S.PubMed
58.
Requejo R, Chouchani ET, Hurd TR, Menger KE, Hampton MB, Murphy MP. Measuring mitochondrial protein thiol redox state. Methods Enzymol. 2010;474:123–47.PubMedCrossRef
Metadaten
Titel
Pristanic Acid Provokes Lipid, Protein, and DNA Oxidative Damage and Reduces the Antioxidant Defenses in Cerebellum of Young Rats
verfasst von
Estela Natacha Brandt Busanello
Vannessa Gonçalves Araujo Lobato
Ângela Zanatta
Clarissa Günther Borges
Anelise Miotti Tonin
Carolina Maso Viegas
Vanusa Manfredini
César Augusto João Ribeiro
Carmen Regla Vargas
Diogo Onofre Gomes de Souza
Moacir Wajner
Publikationsdatum
01.12.2014
Verlag
Springer US
Erschienen in
The Cerebellum / Ausgabe 6/2014
Print ISSN: 1473-4222
Elektronische ISSN: 1473-4230
DOI
https://doi.org/10.1007/s12311-014-0593-0

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