title: Mild hyperhomocysteinemia reduces the activity and immunocontent, but does not alter the gene expression, of catalytic α subunits of cerebral Na+,K+-ATPase.
abstract: Na(+),K(+)-ATPase is a membrane protein which plays a key role in the maintenance of ion homeostasis that is necessary to neuronal excitability, secondary transport and neurotransmitter uptake. Mild hyperhomocysteinemia leads to several clinical manifestations and particularly cerebral diseases; however, little is known about the mechanisms of homocysteine on cerebral Na(+),K(+)-ATPase. In the present study, we investigated the effect of mild hyperhomocysteinemia on the activity, the immunocontent of catalytic subunits (α1, α2, and α3) and the gene expression of this enzyme. We used the experimental model of mild hyperhomocysteinemia that was induced by homocysteine administration (0.03 μmol/g of body weight) twice a day, from the 30th to the 60th postpartum day. Controls received saline in the same volumes. Results showed that mild hyperhomocysteinemia significantly decreased the activity and the immunocontent of the α 1 and α 2 subunits of the Na(+),K(+)-ATPase in cerebral cortex and hippocampus of adult rats. On the other hand, we did not observe any change in levels of Na(+),K(+)-ATPase mRNA transcripts in such cerebral structures of rats after chronic exposure to homocysteine. The present findings support that the homocysteine modulates the Na(+),K(+)-ATPase and this could be associated, at least in part, with the risk to the development of cerebral diseases in individuals with mild hyperhomocysteinemia.
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors: Emilene B S
authors: EB
authors: Scherer
authors: Samanta O
authors: SO
authors: Loureiro
authors: Fernanda C
authors: FC
authors: Vuaden
authors: Felipe
authors: F
authors: Schmitz
authors: Janaína
authors: J
authors: Kolling
authors: Cassiana
authors: C
authors: Siebert
authors: Luiz Eduardo B
authors: LE
authors: Savio
authors: Bruna M
authors: BM
authors: Schweinberger
authors: Maurício R
authors: MR
authors: Bogo
authors: Carla D
authors: CD
authors: Bonan
authors: Angela T S
authors: AT
authors: Wyse
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020134:Catalytic Domain; D002540:Cerebral Cortex / Q000201:enzymology*; D006624:Hippocampus / Q000201:enzymology; D006710:Homocysteine; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000201:enzymology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D006710:Homocysteine; C499075:Atp1a1 protein, rat; C498532:Atp1a2 protein, rat; C541459:Atp1a3 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase