Document Detail


Blockade of ornithine decarboxylase enzyme protects against ischemic brain damage.
MedLine Citation:
PMID:  7929646     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polyamines are derived from ornithine by the actions of ornithine decarboxylase (ODC), which is the rate-limiting step in this pathway. Polyamines play a role in cell growth, neoplasia, differentiation, and response to injury. We have shown that transient cerebral ischemia gives rise to increased ODC mRNA and enzyme activity in the gerbil brain. ODC and polyamines are thought to be important in the generation of edema and the neuronal cell loss associated with cerebral ischemia. To test this theory, we examined the ODC activity, putrescine levels, and neuronal density in the CA1 region of the hippocampus following ischemia and reperfusion injury in the absence and presence of an inhibitor of ODC activity, alpha-difluoromethylornithine (DFMO). Pretreatment of animals with DFMO resulted in attenuation of the ODC activity following 5 min of ischemia and 4 h of reperfusion. In addition, DFMO prevented the increase in polyamine levels, as determined by measurement of putrescine in the ischemic brain. These alterations were not due to changes in ODC mRNA level. Further analysis revealed that DFMO treatment blocked the delayed neuronal cell death in the CA1 region of the hippocampus that accompanies ischemia and reperfusion injury. Administration of DFMO resulted in a dose-dependent beneficial effect upon neuronal cell survival. These results suggest that ODC enzyme activity and the production of polyamines play a significant role in the response of the brain to ischemic injury.
Authors:
M S Kindy; Y Hu; R J Dempsey
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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:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  14     ISSN:  0271-678X     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  1994 Nov 
Date Detail:
Created Date:  1994-11-21     Completed Date:  1994-11-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1040-5     Citation Subset:  IM    
Affiliation:
Sanders Brown Center on Aging, Department of Biochemistry, University of Kentucky Medical Center, Lexington 40536-0084.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain Damage, Chronic / prevention & control*
Brain Ischemia / complications*,  pathology
Cell Survival / drug effects
Eflornithine / pharmacology*
Gerbillinae
Male
Neurons / pathology
Ornithine Decarboxylase / antagonists & inhibitors*,  genetics
Putrescine / antagonists & inhibitors
RNA, Messenger / metabolism
Grant Support
ID/Acronym/Agency:
AG09690/AG/NIA NIH HHS; NS23307/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 110-60-1/Putrescine; 70052-12-9/Eflornithine; EC 4.1.1.17/Ornithine Decarboxylase

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


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