title: Early c-Fos induction after cerebral ischemia: a possible neuroprotective role.
abstract: The role of c-Fos in neurodegeneration or neuroprotection after cerebral ischemia is controversial. To investigate whether early c-Fos induction after ischemia is associated with neuroprotection, rats were subjected to 10 minutes of transient forebrain ischemia and c-Fos expression was examined. Resistant dentate granule cells and neurons in CA2-4 displayed more robust immunoreactivity than vulnerable neurons in the CA1 region of hippocampus during early hours of reperfusion. By 6 hours after reperfusion, c-Fos immunoreactivity was greatly diminished in all areas of the hippocampus. Administration of N-acetyl-O-methyldopamine (NAMDA), a compound previously shown to protect CA1 neurons against ischemia, increased c-Fos immunoreactivity in the CA1 vulnerable region at 6 hours after ischemia and protected SK-N-BE(2)C neurons from oxygen glucose deprivation. Further in vitro study showed that NAMDA potentiated phorbol-12 myristate-13 acetate (PMA)-induced c-Fos expression, AP1 binding activity, and late gene expression determined by chloramphenicol acetyltransferase (CAT) activity from AP1 containing tyrosine hydroxylase promoter-CAT fusion gene in SK-N-BE(2)C neurons. In vivo and in vitro results showed that a neuroprotectant, NAMDA, in concert with another stimulus (for example, ischemia or PMA) up-regulates c-Fos expression and suggested that the early rise of NAMDA-induced c-Fos expression in vulnerable CA1 neurons may account for neuroprotection by means of up-regulating late gene expression for survival.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University at W. M. Burke Medical Research Institute, White Plains, New York 10605, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cho
authors.forename: E M
authors.initials: EM
authors.lastname: Park
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: N
authors.initials: N
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Gal
authors.forename: B T
authors.initials: BT
authors.lastname: Volpe
authors.forename: T H
authors.initials: TH
authors.lastname: Joh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004298:Dopamine / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: C117276:N-acetyl-3-O-methyldopamine; D018696:Neuroprotective Agents; D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D014446:Tyrosine 3-Monooxygenase; D015500:Chloramphenicol O-Acetyltransferase; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen; D004298:Dopamine