Intrastriatal injection of hypoxanthine alters striatal ectonucleotidase activities: a time-dependent effect.
The aim of this study was to investigate the effects of intrastriatal injection of hypoxanthine on ectonucleotidase (E-NTPDases and ecto-5'-nucleotidase) activities and expressions in the striatum of rats. The effect of pre-treatment with vitamins E and C on the effects elicited by this oxypurine on enzymatic activities and on thiobarbituric reactive substances (TBARS) was also investigated. The effect of pre-incubation with hypoxanthine on nucleotide hydrolysis in striatum homogenate was also determined. Adult Wistar rats were divided into (1) control and (2) hypoxanthine-injected groups. For ectonucleotidase activity determination, the animals were sacrificed at 30 min, 24 h and 7 days after drug infusion. For the evaluation of the expression of NTPDase 1-3 and also ecto-5'-nucleotidase, TBARS assay and the influence of the pre-treatment with vitamins on ectonucleotidase activities, the animals were sacrificed 24 h after hypoxanthine infusion. Results show that hypoxanthine infusion significantly inhibited ectonucleotidase activities and increased TBARS only 24 h after administration. Pre-treatment with vitamins was able to prevent these effects. Moreover, ecto-5'-nucleotidase expression was increased (80%) at 24 h after hypoxanthine infusion. We suggest that these hypoxanthine-induced biochemical modifications could, at least in part, participate in the pathophysiology of Lesch Nyhan disease.
Bavaresco
Caren S
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
Kolling
Janaina
J
Ramos
Denise B
DB
Cognato
Giana P
GP
Bonan
Carla D
CD
Bogo
Maurício R
MR
Sarkis
João J F
JJ
Netto
Carlos A
CA
Wyse
Angela T S
AT
D015720:5'-Nucleotidase / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D019271:Hypoxanthine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009711:Nucleotides / Q000378:metabolism; D011755:Pyrophosphatases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology
D015703:Antigens, CD; D002491:Central Nervous System Agents; D009711:Nucleotides; D017392:Thiobarbituric Acid Reactive Substances; D014815:Vitamins; D014810:Vitamin E; D019271:Hypoxanthine; D015720:5'-Nucleotidase; D000251:Adenosine Triphosphatases; D011755:Pyrophosphatases; C027201:ectoATPase; C439652:nucleoside-triphosphate diphosphohydrolase 3; D001081:Apyrase; C067869:CD39 antigen; D001205:Ascorbic Acid