Age-related changes in cerebellar phosphatase-1 reduce Na,K-ATPase activity

Autor(es)

Kawamoto, Elisa Mitiko ^[1] ; Munhoz, Carolina Demarchi ^[1] ; Lepsch, Lucilia Brochado ^[1] ; Lima, Larissa De Sa ^[1] ; Glezer, Isaias ^[1] ; Markus, Regina Pekelmann ^[2] ; Martins de Silva, Claudia Lucia ^[3] ; Camarini, Rosana ^[1] ; Marcourakis, Tania ^[4] ; Scavone, Cristoforo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Biosci Inst, Dept Physiol, BR-05508 Sao Paulo - Brazil

^[3] Univ Fed Rio de Janeiro, Dept Pharmacologym, Rio De Janeiro - Brazil

^[4] Univ Sao Paulo, Dept Clin Chem & Toxicol, Fac Pharmaceut Sci & Neurol, Ctr Invest, FMUSP LIM 15, BR-05508 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEUROBIOLOGY OF AGING; v. 29, n. 11, p. 1712-1720, NOV 2008.
• Citações Web of Science: 7

Resumo

We evaluated whether changes in protein content and activity of PP-1 and PP-2A were the mechanism underneath the basal age-related reduction in alpha(2/3)-Na,K-ATPase activity in rats cerebella and whether this occurred through the cyclic GMP-PKG pathway. PP1 activity, but not its expression, increased with age, whereas PP-2 was not changed. The activity Of ot2/3-Na,K-ATPase varied with age. and there was a negative association between the PP-1 and alpha(2/3)-Na,K-ATPase activities. In young rats, the inhibition of PP-1 and PP-2A by okadaic acid (OA) increased in a dose-dependent manner alpha(1)- and alpha(2/3)-Na,K-ATPase, but had no effect on Mg-ATPase activity. A direct stimulation of PKG with 8-Br-cyclic GMP did not surmount the effect of OA. This analogue of cyclic GMP inhibited PP-1 activity only, indicating that at least part of the increase in alpha(1)- and alpha(2/3)-Na,K-ATPase activity induced by OA was mediated by the cyclic GMP-PKG-PP-1 cascade. Taking into account that PP1 inhibition increased alpha(2/3)-Na,K-ATPase activity, we propose that an age-related increase in PP-1 activity due to a decrease in cyclic GMP-PKG modulation plays a role for the age-related reduction of alpha(2/3)-Na,K-ATPase activity in rat cerebellum. (C) 2007 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 03/08989-0 - MODULACAO DA EXPRESSAO GENICA PELA OUABAINA NO SISTEMA NERVOSO CENTRAL: ENVOLVIMENTO DA Na,K-ATPAse NA MODULACAO DO NF-kB
• Beneficiário: Cristoforo Scavone
• Modalidade de apoio: Auxílio à Pesquisa - Regular