Document Detail


Heparin-binding epidermal growth factor-like growth factor in hippocampus: modulation of expression by seizures and anti-excitotoxic action.
MedLine Citation:
PMID:  9870945     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), an EGF receptor ligand, was investigated in rat forebrain under basal conditions and after kainate-induced excitotoxic seizures. In addition, a potential neuroprotective role for HB-EGF was assessed in hippocampal cultures. In situ hybridization analysis of HB-EGF mRNA in developing rat hippocampus revealed its expression in all principle cell layers of hippocampus from birth to postnatal day (P) 7, whereas from P14 through adulthood, expression decreased in the pyramidal cell layer versus the dentate gyrus granule cells. After kainate-induced excitotoxic seizures, levels of HB-EGF mRNA increased markedly in the hippocampus, as well as in several other cortical and limbic forebrain regions. In the hippocampus, HB-EGF mRNA expression increased within 3 hr after kainate treatment, continued to increase until 24 hr, and then decreased; increases occurred in the dentate gyrus granule cells, in the molecular layer of the dentate gyrus, and in and around hippocampal pyramidal CA3 and CA1 neurons. At 48 hr after kainate treatment, HB-EGF mRNA remained elevated in vulnerable brain regions of the hippocampus and amygdaloid complex. Western blot analysis revealed increased levels of HB-EGF protein in the hippocampus after kainate administration, with a peak at 24 hr. Pretreatment of embryonic hippocampal cell cultures with HB-EGF protected neurons against kainate toxicity. The kainate-induced elevation of [Ca2+]i in hippocampal neurons was not altered in cultures pretreated with HB-EGF, suggesting an excitoprotective mechanism different from that of previously characterized excitoprotective growth factors. Taken together, these results suggest that HB-EGF may function as an endogenous neuroprotective agent after seizure-induced neural activity/injury.
Authors:
L A Opanashuk; R J Mark; J Porter; D Damm; M P Mattson; K B Seroogy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  19     ISSN:  0270-6474     ISO Abbreviation:  J. Neurosci.     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-02-05     Completed Date:  1999-02-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  133-46     Citation Subset:  IM    
Affiliation:
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Epidermal Growth Factor / genetics*
Female
Heparin*
Hippocampus / drug effects,  metabolism*
Intercellular Signaling Peptides and Proteins
Kainic Acid / toxicity
Male
Nerve Degeneration
Neuroprotective Agents / metabolism*
Prosencephalon / drug effects,  metabolism
RNA, Messenger / biosynthesis
Rats
Rats, Sprague-Dawley
Seizures / metabolism*
Grant Support
ID/Acronym/Agency:
AG05119/AG/NIA NIH HHS; NS29001/NS/NINDS NIH HHS; NS35164/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Intercellular Signaling Peptides and Proteins; 0/Neuroprotective Agents; 0/RNA, Messenger; 149176-25-0/heparin-binding EGF-like growth factor; 487-79-6/Kainic Acid; 62229-50-9/Epidermal Growth Factor; 9005-49-6/Heparin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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