Abstract：
:Energy deficiency and dysfunction of the Na,K-ATPase are common consequences of many pathological insults. Glutamate through cyclic GMP and cyclic GMP-dependent protein kinase (PKG) has been shown to stimulate alpha(2/3)-Na,K-ATPase activity in the central nervous system. Thus, a slight impairment of this pathway may amplify the disruption of ion homeostasis in the presence of a non-lethal insult. We investigate the effect of aging (4, 12 and 24 months) on the glutamate-cyclic GMP-PKG modulation of alpha1, alpha(2/3)-Na,K-ATPase activity in rat cerebellum and the stimulation of the glutamate-cyclic GMP-PKG pathway at different levels. Cyclic GMP levels and alpha(2/3)-Na,K-ATPase activity were progressively decreased from 4 and 24 month-old animals. However, PKG basal activity was reduced between 4 and 12 months, and no additional change was observed at 24 months. The ability of 8-Br-cyclic GMP to stimulate PKG activity was only reduced between 12 and 24 months. Moreover, glutamate or 8-Br-cyclic GMP promoted a smaller increase of alpha(2/3)-Na,K-ATPase activity at 24 months, when compared to 4 and 12 months. In spite of the age-related reduced basal levels of cyclic GMP, the production induced by CO or NO was not age-related. Finally, inhibition of PKG activation by KT5823 revealed a lower sensitivity of the enzyme at the older age. Taken together, these data show that basal age-related decline in sodium pump activity is a consequence of changes in different steps of the cyclic GMP-PKG pathway. On the other hand, age-related reduction in glutamate positive modulation of cerebellar alpha(2/3)-Na,K-ATPase is linked to a defective PKG signaling pathway.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Scavone C,Munhoz CD,Kawamoto EM,Glezer I,de Sá Lima L,Marcourakis T,Markus RPdoi
10.1016/j.neurobiolaging.2004.08.013subject
Has Abstractpub_date
2005-06-01 00:00:00pages
907-16issue
6eissn
0197-4580issn
1558-1497pii
S0197-4580(04)00295-7journal_volume
26pub_type
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