title: Modulation of IkappaB kinase autophosphorylation and activity following brain ischemia.
abstract: OBJECTIVE
  To investigate the effects of different antagonists on the alteration of I?B kinase (IKK) activity in rat hippocampus following global brain ischemia.
  
  
  METHODS
  Using 4-vessel occlusion (4-VO) as brain ischemia model, IKK protein expression was examined by immunoblotting and immunoprecipitation, and IKK activity was assayed by in vitro kinase assay.
  
  
  RESULTS
  There was no alteration of IKK protein expression following ischemia or ischemia/reperfusion different time points, but IKK activity reached its peak level at ischemia 30 min. Pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, non-NMDA receptor antagonist DNQX, or NF-kappaB inhibitor PDTC decreased the IKK activity following brain ischemia 30 min. The increase in substrate myelin basic protein (MBP) phosphorylation by IKK is associated with an increase in autophosphorylation of IKK, which can also be antagonized by ketamine, DNQX, and PDTC.
  
  
  CONCLUSIONS
  NMDA receptor and non-NMDA receptor mediate the increase of IKK activity following global brain ischemia in rat hippocampus, which contributes to the alterations of expression and activity of downstream factor NF-kappaB.
authors.affiliation: Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Wan-Hua
authors.initials: WH
authors.lastname: Shen
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Zhang
authors.forename: Guang-Yi
authors.initials: GY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology*; D051550:I-kappa B Kinase; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000201:enzymology*; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016328:NF-kappa B; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; C056723:FG 9041; D007649:Ketamine; D011392:Proline; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase