Effect of neuronal nitric oxide synthase inhibition on Ca2+/calmodulin kinase kinase and Ca2+/calmodulin kinase IV activity during hypoxia in cortical nuclei of newborn piglets

The present study tests the hypothesis that cerebral tissue hypoxia results in increased Ca(2+)/calmodulin (CaM) kinase kinase activity and that the administration of nitric oxide synthase inhibitors (N-nitro-l-arginine [NNLA], or 7-nitroindazole sodium [7-NINA]) prior to the onset of hypoxia will p...

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Published in:Neuroscience 2004, Vol.125 (4), p.937-945
Main Authors: ZUBROW, A. B, DELIVORIA-PAPADOPOULOS, M, FRITZ, K. I, MISHRA, O. P
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - analysis
Adenosine Triphosphate - metabolism
Animals
Animals, Newborn
Biological and medical sciences
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cerebral Cortex - enzymology
Cerebral Cortex - physiopathology
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
Hypoxia - physiopathology
Neurons - drug effects
Neurons - enzymology
Nitric Oxide Synthase - antagonists & inhibitors
Nitric Oxide Synthase - drug effects
Nitric Oxide Synthase Type I
Phosphocreatine - analysis
Phosphocreatine - metabolism
Swine
Vertebrates: nervous system and sense organs
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Summary:The present study tests the hypothesis that cerebral tissue hypoxia results in increased Ca(2+)/calmodulin (CaM) kinase kinase activity and that the administration of nitric oxide synthase inhibitors (N-nitro-l-arginine [NNLA], or 7-nitroindazole sodium [7-NINA]) prior to the onset of hypoxia will prevent the hypoxia-induced increase in the enzyme activity. To test this hypothesis, CaM kinase kinase and CaM kinase IV activities were determined in normoxic, hypoxic, NNLA-treated hypoxic, and 7-NINA-treated hypoxic piglets. Hypoxia was induced (FiO(2)=0.05-0.08x1 h) and confirmed biochemically by tissue levels of ATP and phosphocreatine. CaM kinase kinase activity was determined in a medium containing protein kinase and phosphatase inhibitors, calmodulin, and a specifically designed CaM kinase kinase target peptide. CaM kinase IV activity was determined by (33)P-incorporation into syntide-2 in a buffer containing protein kinase and phosphatase inhibitors. Compared with normoxic animals, ATP and phosphocreatine levels were significantly lower in all hypoxic piglets whether or not pretreated with nitric oxide synthase inhibitors. There was a significant difference among CaM kinase kinase activity (pmol/mg protein/min) in normoxic (76.84+/-14.1), hypoxic (138.86+/-18.2, P
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2004.02.027