Kainic acid induces 14-3-3 zeta expression in distinct regions of rat brain.
Areas of the limbic system of adult male Wistar rats were screened for kainic-acid-induced gene expression. Polymerase-chain-reaction-based differential display identified a 147-bp cDNA fragment, which represented an mRNA that was upregulated in the entorhinal cortex and hippocampus in the kainic-acid-treated animals. The sequence was 97.8% homologous to rat 14-3-3 zeta isoform mRNA. Detailed Northern analysis revealed increased mRNA levels in the entorhinal cortex 1 h after kainic acid exposure and continued elevation 24 h post-injection in both the entorhinal cortex and hippocampus. Western blot analyses confirmed that the protein product of this gene was also present in increased amounts over the same time period. Immunohistochemistry and terminal transferase-mediated dUTP nick end labelling (TUNEL) detected expression of 14-3-3 zeta protein exclusively in the entorhinal cortex and hippocampus, and only in TUNEL-positive neuronal cells. Expression of the tumor suppressor protein, p53 was also induced by kainate injection, and was co-localized with 14-3-3 zeta protein in selected cells only in the affected brain regions. The increase gene expression of 14-3-3 zeta represents a transcription-mediated response associated with region selective neuronal damage induced by kainic acid.
van der Brug
Marcel Patrick
MP
Department of Biochemistry and Molecular Biology, University of Queensland, St. Lucia, 4072, Qld, Brisbane, Australia. marcel@biosci.uq.edu.au
Goodenough
Sharon
S
Wilce
Peter
P
D048948:14-3-3 Proteins; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation; D018076:DNA, Complementary / Q000032:analysis; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid / Q000494:pharmacology*; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
D048948:14-3-3 Proteins; D018076:DNA, Complementary; D018690:Excitatory Amino Acid Agonists; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D014446:Tyrosine 3-Monooxygenase; D007608:Kainic Acid