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Mild hyperhomocysteinemia reduces the activity and immunocontent, but does not alter the gene expression, of catalytic α subunits of cerebral Na+,K+-ATPase

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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 (α 1, α 2, and α 3) 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.

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Acknowledgments

This work was supported in part by grants from Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq–Brazil).

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Authors and Affiliations

  1. Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    Emilene B. S. Scherer, Samanta O. Loureiro, Fernanda C. Vuaden, Felipe Schmitz, Janaína Kolling, Cassiana Siebert, Luiz Eduardo B. Savio, Bruna M. Schweinberger & Angela T. S. Wyse

  2. Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Maurício R. Bogo & Carla D. Bonan

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  1. Emilene B. S. Scherer
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  2. Samanta O. Loureiro
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  3. Fernanda C. Vuaden
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  7. Luiz Eduardo B. Savio
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  11. Angela T. S. Wyse
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Correspondence to Angela T. S. Wyse.

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Scherer, E.B.S., Loureiro, S.O., Vuaden, F.C. et al. Mild hyperhomocysteinemia reduces the activity and immunocontent, but does not alter the gene expression, of catalytic α subunits of cerebral Na+,K+-ATPase. Mol Cell Biochem 378, 91–97 (2013). https://doi.org/10.1007/s11010-013-1598-6

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