Document Detail


Concurrent assessment of calpain and caspase-3 activation after oxygen-glucose deprivation in primary septo-hippocampal cultures.
MedLine Citation:
PMID:  11702043     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The contributions of calpain and caspase-3 to apoptosis and necrosis after central nervous system (CNS) trauma are relatively unexplored. No study has examined concurrent activation of calpain and caspase-3 in necrotic or apoptotic cell death after any CNS insult. Experiments used a model of oxygen-glucose deprivation (OGD) in primary septo-hippocampal cultures and assessed cell viability, occurrence of apoptotic and necrotic cell death phenotypes, and protease activation. Immunoblots using an antibody detecting calpain and caspase-3 proteolysis of alpha-spectrin showed greater accumulation of calpain-mediated breakdown products (BDPs) compared with caspase-3-mediated BDPs. Administration of calpain and caspase-3 inhibitors confirmed that activation of these proteases contributed to cell death, as inferred by lactate dehydrogenase release. Oxygen-glucose deprivation resulted in expression of apoptotic and necrotic cell death phenotypes, especially in neurons. Immunocytochemical studies of calpain and caspase-3 activation in apoptotic cells indicated that these proteases are almost always concurrently activated during apoptosis. These data demonstrate that calpain and caspase-3 activation is associated with expression of apoptotic cell death phenotypes after OGD, and that calpain activation, in combination with caspase-3 activation, could contribute to the expression of apoptotic cell death by assisting in the degradation of important cellular proteins.
Authors:
J K Newcomb-Fernandez; X Zhao; B R Pike; K K Wang; A Kampfl; R Beer; S M DeFord; R L Hayes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  21     ISSN:  0271-678X     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-09     Completed Date:  2001-12-18     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1281-94     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, The Vivian L. Smith Center for Neurologic Research, University of Texas Health Science Center, Houston, Texas, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects,  physiology
Blotting, Western
Calpain / antagonists & inhibitors,  metabolism*
Caspase 3
Caspases / antagonists & inhibitors,  metabolism*
Cells, Cultured
Enzyme Activation / physiology
Enzyme Inhibitors / pharmacology
Fusobacterium Infections
Glucose / pharmacology*
Hippocampus / cytology
Neuroglia / cytology,  drug effects,  enzymology
Neurons / cytology,  drug effects,  enzymology*
Oxygen / pharmacology*
Phenotype
Rats
Reperfusion Injury / enzymology,  pathology
Rosette Formation
Septum of Brain / cytology
Spectrin / metabolism
Stroke / enzymology,  pathology
Grant Support
ID/Acronym/Agency:
R01 NS39091/NS/NINDS NIH HHS; R01 NS40182/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 12634-43-4/Spectrin; 50-99-7/Glucose; 7782-44-7/Oxygen; EC 3.4.22.-/Calpain; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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


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