nach oben

Erschienen in:

01.03.2011 | Original Paper

Homocysteine alters glutamate uptake and Na⁺,K⁺-ATPase activity and oxidative status in rats hippocampus: protection by vitamin C

verfasst von: Fernanda R. Machado, Andréa G. K. Ferreira, Aline A. da Cunha, Bárbara Tagliari, Ben Hur M. Mussulini, Susana Wofchuk, Angela T. S. Wyse

Erschienen in: Metabolic Brain Disease | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

In the present study we investigate the effect of homocysteine on glutamate uptake, Na⁺,K⁺-ATPase, enzymatic antioxidant defenses, as well as reactive species levels in hippocampus of rats. The influence of vitamin C, a classic antioxidant, on the effects elicited by homocysteine was also tested. Results showed that chronic hyperhomocysteinemia decreased glutamate uptake and the activities of Na⁺,K⁺-ATPase, catalase and superoxide dismutase in hippocampus of rats. Reactive species levels were increased by chronic homocysteine administration. Concomitant administration of vitamin C significantly prevented these alterations caused by homocysteine. According to our results, it seems possible to suggest that the reduction in glutamate uptake and Na⁺,K⁺-ATPase activity may be mediated by oxidative stress, since vitamin C prevented these effects. We suggest that the administration of antioxidants should be considered as an adjuvant therapy to specific diet in homocystinuria.

Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126PubMedCrossRef

Banhegyi G, Braun L, Csala M, Puskas F, Mandl J (1997) Ascorbate metabolism and its regulation in animals. Free Radic Biol Med 23:793–803PubMedCrossRef

Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-die-binding. Anal Biochem 72:248–254PubMedCrossRef

Brömme H-J, Zühlke L, Silber R-H, Simm A (2008) DCFH2 interactions with hydroxyl radicals and other oxidants—influence of organic solvents. Exp Gerontol 43:638–644PubMedCrossRef

Buettner GR, Jurkiewicz BA (1996) Catalytic metals, ascorbate and free radicals: combinations to avoid. Radiat Res 145:532–541PubMedCrossRef

Cascalheira JF, Parreira MC, Viegas AN, Faria MC, Domingues FC (2008) Serum homocysteine: relationship with circulating levels of cortisol and ascorbate. Ann Nutr Metab 53:67–74PubMedCrossRef

Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS (1999) Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 99:1156–1160PubMed

Chan KM, Delfert D et al (1986) A direct colorimetric assay for Ca2+-stimulated ATPase activity. Anal Biochem 157:375–380PubMedCrossRef

Chen Q, Espey MG, Sun AY, Lee JH, Krishna MC, Shacter E et al (2007) Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci USA 104:8749–8754PubMedCrossRef

Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC et al (2008) Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci USA 105:11105–11109PubMedCrossRef

Collingridge GL, Lester RAJ (1989) Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol Rev 40:143–210

Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105PubMedCrossRef

Dayal S, Arning E, Bottiglieri T, Boger RH, Sigmund CD, Faraci FM, Lentz SR (2004) Cerebral vascular dysfunction mediated by superoxide in hyperhomocysteinemic mice. Stroke 35:1957–1962PubMedCrossRef

Englard S, Seifter S (1986) The biochemical functions of ascorbic acid. Annu Rev Nutr 6:365–406PubMedCrossRef

Faraci FM, Lentz SR (2004) Hyperhomocysteinemia, oxidative stress, and cerebral vascular dysfunction. Stroke 35:345–347PubMedCrossRef

Fonnum F (1984) Glutamate: a neurotransmitter in mammalian brain. J Neurochem 42:1–11PubMedCrossRef

Fox BA, Cameron AG (1989) In: Arnold E (ed) Food science. Nutrition and Health, London

Frizzo ME, Lara DR et al (2002) Guanosine enhances glutamate uptake in brain cortical slices at normal and excitotoxic conditions. Cell Mol Neurobiol 22:353–363PubMedCrossRef

Gallucci M, Zanardo A, De Valentin L, Vianello A (2004) Homocysteine in Alzheimer disease and vascular dementia. Arch Gerontol Geriatr Suppl 9:195–200PubMedCrossRef

Headley PM, Grillner S (1990) Excitatory amino acids and synaptic transmission: the evidence for a physiological function. Trends Pharmacol Sci 11:205–211PubMedCrossRef

Herrmann W, Lorenzl S, Obeid R (2007) Review of the role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric disorders—current evidence and preliminary recommendations. Fortschr Neurol Psychiatr 75:515–527PubMedCrossRef

Hitschke K, Buhler R, Apell HJ, Stark G (1994) Inactivation of the Na+, K+-ATPase by radiation-induced free radicals. Evidence for a radical-chain mechanism. FEBS Lett 353:297–300PubMedCrossRef

Kuhn W, Roebroek R, Blom H, Van Oppenraaj D, Przuntek H, Kretschmer A, Buttner T, Woitalla D, Muller T (1998) Elevated plasma levels of homocysteine in Parkinson’s disease. Eur Neurol 40:225–227PubMedCrossRef

Lebel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′, 7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231PubMedCrossRef

Lees GJ (1993) Contributory mechanisms in the causation of neurodegenerative disorders. Neuroscience 54:287–322PubMedCrossRef

Lipton SA, Kim WK, Choi YB, Kumar S, D’Emilia DM, Rayudu PV, Arnelle DR, Stamler JS (1997) Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA 94:5923–5928PubMedCrossRef

Lowry OH, Rosebrough NJ, Farr AL, RandalL RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–267PubMed

Marklund SL (1985) Pyrogallol autoxidation. In: Handbook for oxygen radical research. CRC Press, Boca Raton, pp 243–247

Matté C, Mackedanz V, Stefanello FM, Scherer EB, Andreazza AC, Zanotto C, Moro AM, Garcia SC, Gonçalves CA, Erdtmann B, Salvador M, Wyse AT (2009a) Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid. Neurochem Int 54:7–13PubMedCrossRef

Matté C, Stefanello FM, Mackedanz V, Pederzolli CD, Lamers ML, Dutra-Filho CS, Dos Santos MF, Wyse AT (2009b) Homocysteine induces oxidative stress, inflammatory infiltration, fibrosis and reduces glycogen/glycoprotein content in liver of rats. Int J Dev Neurosci 27:337–344PubMedCrossRef

Matté C, Mussulini BH, Dos Santos TM, Soares FM, Simão F, Matté A, De Oliveira DL, Salbego CG, Wofchuk ST, Wyse AT (2010) Hyperhomocysteinemia reduces glutamate uptake in parietal cortex of rats. Int J Dev Neurosci 28:183–187PubMedCrossRef

Mattson MP, Chan SL, Duan W (2002) Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev 82:637–672PubMed

Mudd SH, Levy HL, Skovby F (2001) Disorders of transsulfuration. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular basis of inherited disease. McGraw-Hill, New York, pp 1279–1327

Pari L, Murugavel P (2007) Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats. Toxicology 234:44–50PubMedCrossRef

Peterkofsky B (1991) Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr 54:1135–1140

Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356PubMedCrossRef

Potts MB, Koh SE, Whetstone WD, Walker BA, Yoneyama T, Claus CP, Manvelyan HM, Noble-Haeusslein LJ (2006) Traumatic injury to the immature brain: inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets. NeuroRx 3:143–153PubMedCrossRef

Radi R, Beckman JS, Bush KM, Freeman BA (1991) Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J Biol Chem 266:4244–4250PubMed

Rose RC, Bode AM (1993) Biology of free radical scavangers: an evaluation of ascorbate. FASEB J 7:1135–1142PubMed

Rose EM, Koo JC, Antflick JE, Ahmed SM, Angers S, Hampson DR (2009) Glutamate transporter coupling to Na,K-ATPase. J Neurosci 29:8143–8155PubMedCrossRef

Sachdev PS (2004) Homocysteine and neuropsychiatric disorders. Rev Bras Psiquiatr 26:50–56PubMedCrossRef

Schalinske KL (2009) Hepatic sulfur amino acid metabolism. In: Masella R, Mazza G (eds) Glutathione and sulfur amino acids in human health and disease. Wiley, Hoboken, pp 73–90CrossRef

Scriver CR, Beaudet AL, Sly WS, Valle D (2001) The metabolic & molecular bases of inherited disease. McGraw-Hill, New York

Sheldon AL, Robinson MB (2007) The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. Neurochem Int 51:333–355PubMedCrossRef

Siems WG, Hapner SJ, van Kuijk FJ (1996) 4-hydroxynonenal inhibits Na+,K+-ATPase. Free Radic Biol Med 20:215–223PubMedCrossRef

Sjöström M, Stenström K, Eneling K, Zwiller J, Katz AI, Takemori H, Bertorello AM (2007) SIK1 is part of a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process. Proc Natl Acad Sci USA 104:16922–16927PubMedCrossRef

Streck EL, Matte C et al (2002) Reduction of Na+,K+-ATPase activity in hippocampus of rats subjected to chemically induced hyperhomocysteinemia. Neurochem Res 27:1593–1598PubMedCrossRef

Streck EL, Vieira PS, Wannmacher CM, Dutra-Filho CS, Wajner M, Wyse AT (2003) In vitro effect of homocysteine on some parameters of oxidative stress in rat hippocampus. Metab Brain Dis 18:147–154PubMedCrossRef

Streck EL, Bavaresco CS, Netto CA, Wyse AT (2004) Chronic hyperhomocysteinemia provokes a memory deficit in rats in the Morris water maze task. Behav Brain Res 153:377–381PubMedCrossRef

Upchurch GR Jr, Welch GN, Fabian AJ, Freedman JE, Johnson JL Jr, Keaney JF, Loscalzo J (1997) Homocysteine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 272:17012–17017PubMedCrossRef

Volterra A, Trotti D, Racagni G (1994) Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechanisms. Mol Pharmacol 46:986–992PubMed

White AR, Huang X, Jobling MF, Barrow CJ, Beyreuther K, Masters CL, Bush AL, Cappai R (2001) Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures possible risk factors in the Alzheimer’s-type neurodegenerative pathways. J Neurochem 76:1509–1520PubMedCrossRef

Wyse AT, Streck EL et al (2000) Preconditioning prevents the inhibition of Na+,K+-ATPase activity after brain ischemia. Neurochem Res 25:971–975CrossRef

Wyse AT, Zugno AI, Streck EL, Matté C, Calcagnotto T, Wannmacher CMD, Wajner M (2002) Inhibition of Na+,K+-ATPase activity in hippocampus of rats subjected to acute administration of homocysteine is prevented by vitamins E and C treatment. Neurochem Res 27:1685–1689PubMedCrossRef

Yamamato M, Hara H, Adachi T (2000) Effects of homocysteine on the binding of extracellular-superoxide dismutase to the endothelial cell surface. FEBS Lett 486:159–162CrossRef

Zieminska E, Lazarewicz JW (2006) Excitotoxic neuronal injury in chronic homocysteine neurotoxicity studied in vitro: the role of NMDA and group I metabotropic glutamate receptors. Acta Neurobiol Exp Wars 66:301–309PubMed

Titel: Homocysteine alters glutamate uptake and Na+,K+-ATPase activity and oxidative status in rats hippocampus: protection by vitamin C
verfasst von: Fernanda R. Machado
Andréa G. K. Ferreira
Aline A. da Cunha
Bárbara Tagliari
Ben Hur M. Mussulini
Susana Wofchuk
Angela T. S. Wyse
Publikationsdatum: 01.03.2011
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 1/2011
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-011-9232-3

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Schwindelursache: Massagepistole lässt Otholiten tanzen

14.05.2024 Benigner Lagerungsschwindel Nachrichten

Wenn jüngere Menschen über ständig rezidivierenden Lagerungsschwindel klagen, könnte eine Massagepistole der Auslöser sein. In JAMA Otolaryngology warnt ein Team vor der Anwendung hochpotenter Geräte im Bereich des Nackens.

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Viertel reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2011

Peripheral immune challenge with dsRNA enhances kainic acid-induced status epilepticus

Neurological disorders associated with cassava diet: a review of putative etiological mechanisms

Effects of flavonoids on glycosaminoglycan synthesis: implications for substrate reduction therapy in Sanfilippo disease and other mucopolysaccharidoses

In vivo neuroprotective effect of L-carnitine against oxidative stress in maple syrup urine disease

Prevention of cerebral ischemia-induced memory deficits by inhibition of phosphodiesterase-4 in rats