Effect of hypoxanthine on Na+,K+-ATPase activity and some parameters of oxidative stress in rat striatum.
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.
Bavaresco
Caren Serra
CS
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.
Chiarani
Fabria
F
Matté
Cristiane
C
Wajner
Moacir
M
Netto
Carlos Alexandre
CA
de Souza Wyse
Angela Terezinha
AT
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
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