Hypoxia induces activation of a N-methyl-D-aspartate glutamate receptor-protein kinase C pathway in the dorsocaudal brainstem of the conscious rat.
To study in vivo phosphorylation of N-methyl-D-aspartate (NMDA) glutamate receptors and the recruitment of protein kinase C isoforms during acute hypoxia, dorsocaudal brainstem lysates were harvested from conscious rats exposed to either room air or hypoxia (10% O2 for 5 and 15 min). Increased phosphorylation of the NR-1 subunit at serine residue 896 occurred during hypoxia and was blocked by pre-treatment with MK-801. Immunoblots of soluble and particulate fractions revealed subcellular translocation for PKC-beta, -gamma, -delta, -epsilon, and -iota during hypoxia with no changes in PKC-alpha, -mu, and -zeta. Translocation of PKC-beta, -delta and -epsilon was selectively attenuated following MK-801. We demonstrate that hypoxia leads to PKC-mediated activation of NMDA receptors in the brainstem, and that PKC-beta, -delta and -epsilon are the most likely candidates for NR-1 phosphorylation.
Simakajornboon
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Department of Pediatrics, Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Gozal
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Gozal
Y M
YM
Gozal
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D
D000818:Animals; D001692:Biological Transport; D001933:Brain Stem / Q000378:metabolism*; D003243:Consciousness; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004789:Enzyme Activation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D007527:Isoenzymes / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction
D018691:Excitatory Amino Acid Antagonists; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D011493:Protein Kinase C