Age-related changes in cerebellar phosphatase-1 reduce Na,K-ATPase activity.
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 alpha(2/3)-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.
Kawamoto
Elisa Mitiko
EM
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, Avenida Lineu Prestes, 1524, 05508-900 São Paulo, Brazil.
Munhoz
Carolina Demarchi
CD
Lepsch
Lucília Brochado
LB
de Sá Lima
Larissa
L
Glezer
Isaias
I
Markus
Regina Pekelmann
RP
de Silva
Claudia Lucia Martins
CL
Camarini
Rosana
R
Marcourakis
Tania
T
Scavone
Cristoforo
C
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002531:Cerebellum / Q000201:enzymology*; D004789:Enzyme Activation; D008297:Male; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D054645:Protein Phosphatase 1; D000254:Sodium-Potassium-Exchanging ATPase