Nitric oxide-mediated Ca2+/calmodulin-dependent protein kinase IV activity during hypoxia in neuronal nuclei from newborn piglets

The present study tested the hypothesis that hypoxia results in increased Ca2+/calmodulin-dependent protein kinase IV (CaM kinase IV) activity and that inhibition of nitric oxide (NO) synthase by N-nitro-L-arginine (NNLA) prevents the hypoxia-induced increase in neuronal nuclear CaM kinase IV activity in newborn piglets. CaM kinase IV activity was determined in normoxic (Nx), hypoxic (Hx), and NNLA-pretreated Hx piglets. Cerebral hypoxia was confirmed biochemically. There was a significant difference between CaM kinase IV activity (pmoles/mg protein/min) in Nx (285.22 +/- 86.12), Hx (494.77 +/- 99.79, P < 0.05 vs. Nx), and NNLA-pretreated Hx (249.55 +/- 53.85)(P = NS vs. Nx, P < 0.05 vs. Hx) animals. The results demonstrate that the cerebral tissue hypoxia results in an increase in neuronal nuclear CaM kinase IV activity, and the hypoxia-induced increase in CaM kinase IV activity is NO-mediated. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.