Document Detail


Evolution of GADD34 expression after focal cerebral ischaemia.
MedLine Citation:
PMID:  15713259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
GADD34, a stress response protein associated with cell rescue, DNA repair and apoptosis, is expressed in the ischaemic brain. The C-terminal region of GADD34 has homology with the Herpes Simplex Virus protein, ICP34.5, which overcomes the protein synthesis block after viral infection by actively dephosphorylating eukaryotic translation initiation factor 2alpha (eIF2alpha). The carboxy terminus of GADD34 is also capable of dephosphorylating eIF2alpha and therefore has the capacity to restore the protein synthesis shutoff associated with ischaemia. This study examines the distribution and time course of GADD34 expression after focal cerebral ischaemia. Focal ischaemia or sham procedure was carried out on Sprague-Dawley rats with survival times of 4, 12, 24 h, 7 and 30 days. Brains were processed for histology and immunohistochemistry. Ischaemic damage was mapped onto line diagrams and GADD34 positive cells counted in selected regions of cortex and caudate. GADD34 immunopositive cells (mainly neurones), expressed as cells/mm2, were present in ischaemic brains at 4 h (e.g., peri-infarct cortex 20 +/- 5; contralateral cortex 3 +/- 1, P < 0.05). Of the time points examined, numbers of GADD34 positive cells were highest 24 h after ischaemia (peri-infarct cortex 31 +/- 7.3, contralateral cortex 0.1 +/- 0.1, P < 0.05). Immunopositive cells, following a similar time course, were identified within the peri-infarct zone in the caudate nucleus and in ipsilateral cingulate cortex (possibly as a consequence of cortical spreading depression). GADD34 positive cells did not co-localise with a marker of irreversible cell death (TUNEL). Taken together, GADD34 positive cells in key neuroanatomical locations pertinent to the evolving ischaemic lesion, the lack of co-localisation with TUNEL and the protein's known effects on restoring protein synthesis, repairing DNA and involvement in ischaemic pre-conditioning suggests that it has the potential to influence cell survival in ischaemically compromised tissue.
Authors:
David McCaig; Hideaki Imai; Lindsay Gallagher; David I Graham; June Harland; S Moira Brown; I Mhairi Macrae
Related Documents :
19267409 - Fibroblast growth factor-9 inhibits astrocyte differentiation of adult mouse neural pro...
19304959 - Ptpmu suppresses glioma cell migration and dispersal.
18333959 - Impact of sex and hormones on new cells in the developing rat hippocampus: a novel sour...
18322099 - Early neuronal and glial fate restriction of embryonic neural stem cells.
6620429 - Factors in manifestation of developmental abnormalities of the central nervous system b...
15602759 - Culturing primary brain astrocytes under a fully controlled environment in a novel bior...
19774649 - 5-aminosalicylic acid interferes in the cell cycle of colorectal cancer cells and induc...
20539739 - Normal levels of p27 are necessary for somite segmentation and determining pronephric o...
19648159 - Surface translocation and tri-iodothyronine uptake of mutant mct8 proteins are cell typ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  1034     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-16     Completed Date:  2005-05-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  51-61     Citation Subset:  IM    
Affiliation:
Wellcome Surgical Institute, Division of Clinical Neuroscience, University of Glasgow, Garscube Estate, Bearsden Road, Glasgow G61 1QH, UK.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Brain / enzymology*,  pathology,  physiopathology
Brain Ischemia / enzymology*,  pathology,  physiopathology
Brain Mapping
Caudate Nucleus / enzymology,  pathology,  physiopathology
Cell Death / physiology
Cell Survival / physiology
Cerebral Infarction / enzymology*,  pathology,  physiopathology
DNA Repair / physiology
Disease Models, Animal
Disease Progression
Gyrus Cinguli / enzymology,  pathology,  physiopathology
Immunohistochemistry
Infarction, Middle Cerebral Artery / enzymology,  pathology,  physiopathology
Male
Neocortex / enzymology,  pathology,  physiopathology
Nerve Degeneration / enzymology*,  pathology,  physiopathology
Neurons / enzymology*,  pathology
Proteins / metabolism*
Rats
Rats, Sprague-Dawley
Time Factors
Up-Regulation / physiology
Chemical
Reg. No./Substance:
0/Proteins

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


Previous Document:  Properties of presynaptic P2X7-like receptors at the neuromuscular junction.
Next Document:  Spontaneous muscle action potentials are blocked by N-type and P/Q-calcium channels blockers in the ...