Neurochemical research
-
Neurochemical research · Dec 2006
Nuclear Ca(++)-influx, Ca (++)/calmodulin-dependent protein kinase IV activity and CREB protein phosphorylation during post-hypoxic reoxygenation in neuronal nuclei of newborn piglets: the role of nitric oxide.
The present study tests the hypothesis that post-hypoxic reoxygenation results in an nitric oxide (NO)-mediated increase in nuclear Ca(++)-influx, increased calmodulin kinase (CaM kinase) IV activity, and increased Ser(133) phosphorylation of cyclic AMP response element binding (CREB) protein in neuronal nuclei of the cerebral cortex of newborn piglets. Piglets were divided into normoxic (Nx), hypoxic (Hx, FiO(2) = 0.07 for 1 h), hypoxic with 6 h reoxygenation (Hx + reox), and Hx + reox injected with 7-nitroindazole sodium salt (7-NINA), a nNOS inhibitor, immediately after hypoxia (Hx + 7-NINA). Cerebral tissue hypoxia was documented by ATP and phosphocreatine (PCr) levels. ⋯ We conclude that post-Hx increase in nuclear Ca(++)-influx leading to increased phosphorylation of CREB protein is mediated by NO derived from nNOS. However, hypoxia-induced increase in CaM Kinase IV activity decreased during the post-Hx reox. We propose that hypoxia-induced increase in CaM Kinase IV activity leads to increased phosphorylation of CREB protein and transcription of proapoptotic genes during post-Hx reox resulting in Hx neuronal death.