Developmental patterns of NF-kappaB activation during acute hypoxia in the caudal brainstem of the rat.
NF-kappaB, an ubiquitous transcription factor which plays a major role in the regulation of stress-related genes, is activated during environmental hypoxia in the dorsocaudal brainstem of adult rats. To examine the developmental pattern of NF-kappaB basal activity in the brainstem and the response to hypoxia, electromobility shift assays and immunohistochemical staining for the P65 subunit of NF-kappaB were performed in caudal brainstem samples of rats at 2, 5, 10, 15, and 60 days postnatal age, following normoxic or hypoxic (1 h in 10% O2) exposures. In addition, the expression of IkappaB-alpha, and IkappaB kinases (ikk)-alpha and -beta was also examined using Western blots. Basal NF-kappaB nuclear activity and nuclear P65 immunoreactivity increased with maturation. In contrast, hypoxia induced enhanced activation of NF-kappaB and nuclear translocation of P65 in youngest animals. Expression of both IkappaB-alpha and ikk-alpha was highest in the more immature rats, and decreased with postnatal age. In contrast, ikk-beta expression was unchanged over time. We conclude that NF-kappaB activity in caudal brainstem is developmentally regulated, and that hypoxia-induced NF-kappaB activation is more prominent in youngest rats. We postulate that postnatal regulation of NF-kappaB complex expression and function may underlie fundamental genomic processes mediating developmental changes in neuronal hypoxic tolerance.
Simakajornboon
N
N
Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Gozal
E
E
Gozal
D
D
D000208:Acute Disease; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D004586:Electrophoresis; D005260:Female; D002534:Hypoxia, Brain / Q000378:metabolism*; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D007150:Immunohistochemistry; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism; D051381:Rats
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase