A significant increase in both basal and maximal calcineurin activity in the rat pilocarpine model of status epilepticus.
This study focused on the effects of status epilepticus on the activity of calcineurin, a neuronally enriched, calcium-dependent phosphatase. Calcineurin is an important modulator of many neuronal processes, including learning and memory, induction of apoptosis, receptor function and neuronal excitability. Therefore, a status epilepticus-induced alteration of the activity of this important phosphatase would have significant physiological implications. Status epilepticus was induced by pilocarpine injection and allowed to continue for 60 min. Brain region homogenates were then assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant status epilepticus-dependent increase in both basal and Mn(2+)-dependent calcineurin activity was observed in homogenates isolated from the cortex and hippocampus, but not the cerebellum. This increase was resistant to 150 nM okadaic acid, but sensitive to 50 microM okadaic acid. The increase in basal activity was also resistant to 100 microM sodium orthovanadate. Both maximal dephosphorylation rate and substrate affinity were increased following status epilepticus. However, the increase in calcineurin activity was not found to be due to an increase in calcineurin enzyme levels. Finally, increase in calcineurin activity was found to be NMDA-receptor activation dependent. The data demonstrate that status epilepticus resulted in a significant increase in both basal and maximal calcineurin activity.
Kurz
J E
JE
Department of Biology, Virginia Commonwealth University, Richmond, Virginia, USA.
Sheets
D
D
Parsons
J T
JT
Rana
A
A
Delorenzo
R J
RJ
Churn
S B
SB
D000818:Animals; D001921:Brain / Q000201:enzymology*; D019703:Calcineurin / Q000378:metabolism*; D002540:Cerebral Cortex / Q000201:enzymology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology; D007700:Kinetics; D008297:Male; D009596:Nitrophenols / Q000378:metabolism; D009928:Organ Specificity; D009943:Organophosphorus Compounds / Q000378:metabolism; D010862:Pilocarpine; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013226:Status Epilepticus / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D013379:Substrate Specificity
D009596:Nitrophenols; D009943:Organophosphorus Compounds; D010862:Pilocarpine; C008644:nitrophenylphosphate; D016291:Dizocilpine Maleate; D019703:Calcineurin; D017027:Protein Tyrosine Phosphatases