title: Effect of hypoxanthine on Na+,K+-ATPase activity and some parameters of oxidative stress in rat striatum.
abstract: The main objective of this study was to investigate the effects of preincubation of rat striatum homogenate in the presence of hypoxanthine, a metabolite accumulated in Lesch-Nyhan disease, on Na+,K+-ATPase activity and on some parameters of oxidative stress namely thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant parameter (TRAP) and membrane protein thiol content. Results showed that hypoxanthine significantly increased TBA-RS and reduced Na+,K+-ATPase activity, TRAP and membrane protein thiol content. In addition, we also evaluated the effect of glutathione, trolox, allopurinol and Nvarpi-nitro-L-arginine methyl ester (L-NAME) on the inhibitory effect of hypoxanthine on Na+,K+-ATPase activity in the same rat cerebral structure. All tested compounds per se did not alter Na+,K+-ATPase activity, but only glutathione and trolox prevented the effect of hypoxanthine on the enzyme activity. The effect of glutathione and trolox on hypoxanthine-induced increase of TBA-RS levels was also investigated. These antioxidants alone or combined with hypoxanthine reduced TBA-RS levels. Our present findings show that hypoxanthine induces oxidative stress in rat striatum and that the inhibition of Na+,K+-ATPase activity caused by this oxypurine was probably mediated by reactive oxygen species. It is presumed that these results might be associated with the neuronal dysfunction of patients affected by Lesch-Nyhan disease.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Caren Serra
authors.initials: CS
authors.lastname: Bavaresco
authors.forename: Fabria
authors.initials: F
authors.lastname: Chiarani
authors.forename: Cristiane
authors.initials: C
authors.lastname: Matté
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: Netto
authors.forename: Angela Terezinha
authors.initials: AT
authors.lastname: de Souza Wyse
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D019271:Hypoxanthine / Q000494:pharmacology*; D007926:Lesch-Nyhan Syndrome / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008959:Models, Neurological; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism; D013347:Subcellular Fractions; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects / Q000201:enzymology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005609:Free Radicals; D008565:Membrane Proteins; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D019271:Hypoxanthine; D000254:Sodium-Potassium-Exchanging ATPase