NF-kappaB induction during in vivo hypoxia in dorsocaudal brain stem of rat: effect of MK-801 and L-NAME.
In the nucleus of the solitary tract, NMDA receptors are critical for the hypoxic ventilatory response while neuronal nitric oxide synthase (NOS) modulates the late component of this response. Nuclear factor (NF)-kappaB is a ubiquitous transcription factor that increases the expression of multiple stress-activated genes. We sought to examine temporal changes in expression of NF-kappaB within the dorsocaudal brain stem of conscious rats after exposures to 10% O2. Time-dependent increases in NF-kappaB occurred with hypoxia and peaked at 60 min. Pretreatment with the N-methyl-D-aspartate (NMDA)-receptor channel antagonist dizocilpine maleate (MK-801) markedly attenuated NF-kappaB complexes during hypoxia. In contrast, after NOS inhibition with NG-nitro-L-arginine methyl ester (L-NAME), although NF-kappaB was diminished in normoxia, increased NF-kappaB expression still occurred with hypoxia. Increased phosphorylation of the NF-kappaB regulatory unit [inhibitory (I)kappaB] was detected by immunoblotting and also peaked at 60 min. Phosphorylation of Ikappa-B during hypoxia was attenuated by MK-801 but not by L-NAME. Thus NMDA-receptor activation in the dorsocaudal brain stem during hypoxia elicits in NF-kappaB activity marked enhancements that are unaffected after NOS blockade.
Gozal
E
E
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. dgozal@tmcpop.tmc.tulane.edu
Simakajornboon
N
N
Gozal
D
D
D000818:Animals; D015153:Blotting, Western; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis* / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016328:NF-kappa B; D016291:Dizocilpine Maleate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester