Document Detail


Calpain and N-methyl-d-aspartate (NMDA)-induced excitotoxicity in rat retinas.
MedLine Citation:
PMID:  15878434     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Calpain-mediated proteolysis has been implicated as a major process in neuronal cell death in both acute insults and the chronic neurodegenerative disorders in the central nerves system. However, activation of calpain also plays a protective function in the early phase of excitotoxic neuronal death. The exact role of calpains in neuronal death and recovery after exposure to N-methyl-D-aspartate (NMDA) is not clearly known. The purpose of present study was to examine the involvement of mu- and m-calpain in NMDA-induced excitotoxicity in the adult rat retina. Increased immunoreactivity of mu-calpain was noted in RGC layer cells and in the inner nuclear layer with maximal expression at 12 h after NMDA injection. This was further confirmed with Western blotting. TdT-mediated biotin-dUTP nick end labeling (TUNEL) positive cells in the inner retina co-localized with moderate or intense mu-calpain immunoreactivity. In contrast, there was no remarkable change in m-calpain immunoreactivity at any time point after NMDA injection. Simultaneous injection of 2 nmol of a calpain inhibitor (calpain inhibitor II) significantly reduced the number of TUNEL-positive cells in the inner retina at 18 h after NMDA injection and preserved RGC-like cells counted at 7 days after injection. The results of this study showed that mu-calpain may be involved in mediating NMDA-induced excitotoxicity in the rat retina and calpain inhibitors may play a therapeutic role in NMDA related disease.
Authors:
Kin Chiu; Tim Tak Lam; Winnie Wai Ying Li; Joseph Caprioli; Jacky Man Kwong Kwong
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  1046     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-01     Completed Date:  2005-09-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  207-15     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects,  physiology*
Blotting, Western
Calpain / metabolism*
DNA Fragmentation / drug effects,  physiology
Immunohistochemistry
In Situ Nick-End Labeling
Isoenzymes
Male
N-Methylaspartate
Neurons / drug effects,  enzymology*
Neurotoxins
Rats
Rats, Sprague-Dawley
Retina / drug effects,  enzymology*,  pathology
Retinal Diseases / chemically induced,  enzymology*
Chemical
Reg. No./Substance:
0/Isoenzymes; 0/Neurotoxins; 6384-92-5/N-Methylaspartate; EC 3.4.22.-/Calpain; EC 3.4.22.-/m-calpain; EC 3.4.22.-/mu-calpain

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