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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 10
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: NEUROBIOLOGY OF AGING; v. 29, n. 11, p. 1712-1720, NOV 2008.
Web of Science Citations: 7
Abstract

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)