title: Mild hyperhomocysteinemia alters extracellular adenine metabolism in rat brain.
abstract: Since homocysteine (Hcy) is considered a risk factor to cerebral diseases and adenine nucleotides are important molecules to brain normal function, in the present study we investigated the effect of chronic mild hyperhomocysteinemia on ectonucleotidase activities and expression in rat cerebral cortex. The levels of ATP, ADP, AMP and adenosine (Ado) in cerebrospinal fluid (CSF) of adult rats also were evaluated by high-performance liquid chromatography. For the chronic chemically induced mild hyperhomocysteinemia, Hcy (0.03 μmol/g of body weight) was administered subcutaneously from the 30th to the 60th day of life. Control rats received saline solution in the same volumes. Results showed that Hcy significantly decreased nucleotide hydrolysis in the synaptosomal fraction and increased E-NTPDase1 and ecto-5'-nucleotidase transcripts in rat cerebral cortex. ATP levels were significantly increased, while Ado decreased in CSF of Hcy-treated rats. These findings suggest that the unbalance in ATP and Ado levels may be, at last in part, involved in the cerebral toxicity of mild hyperhomocysteinemia.
authors.affiliation: Laboratório de Neuroproteção e Doenças Neurometabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: E B S
authors.initials: EB
authors.lastname: Scherer
authors.forename: F
authors.initials: F
authors.lastname: Schmitz
authors.forename: F C
authors.initials: FC
authors.lastname: Vuaden
authors.forename: L E B
authors.initials: LE
authors.lastname: Savio
authors.forename: A G K
authors.initials: AG
authors.lastname: Ferreira
authors.forename: R A J C
authors.initials: RA
authors.lastname: Tasca
authors.forename: E A
authors.initials: EA
authors.lastname: Casali
authors.forename: M R
authors.initials: MR
authors.lastname: Bogo
authors.forename: C D
authors.initials: CD
authors.lastname: Bonan
authors.forename: A T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism; D000225:Adenine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D045604:Extracellular Fluid / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D020138:Hyperhomocysteinemia / Q000378:metabolism / Q000473:pathology*; D011687:Purines / Q000134:cerebrospinal fluid; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism / Q000473:pathology; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D058851:GPI-Linked Proteins; D011687:Purines; D012333:RNA, Messenger; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; C548243:Nt5e protein, rat; D000251:Adenosine Triphosphatases; D000225:Adenine; C030985:purine