Document Detail


A novel calpastatin-based inhibitor improves postischemic neurological recovery.
MedLine Citation:
PMID:  19422795     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Calpastatin, a naturally occurring protein, is the only inhibitor that is specific for calpain. A novel blood-brain barrier (BBB)-permeant calpastatin-based calpain inhibitor, named B27-HYD, was developed and used to assess calpain's contribution to neurological dysfunction after stroke in rats. Postischemic administration of B27-HYD reduced infarct volume and neurological deficits by 35% and 44%, respectively, compared to untreated animals. We also show that the pharmacologic intervention has engaged the intended biologic target. Our data further demonstrates the potential utility of SBDP145, a signature biomarker of acute brain injury, in evaluating possible mechanisms of calpain in the pathogenesis of stroke and as an adjunct in guiding therapeutic decision making.
Authors:
John Anagli; Yuxia Han; Laura Stewart; Dongmei Yang; Ashkhen Movsisyan; Kadija Abounit; Donald Seyfried
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-05
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  385     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-08     Completed Date:  2009-06-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  94-9     Citation Subset:  IM    
Affiliation:
Department of Pathology, Henry Ford Hospital, 1 Ford Place, 5D, Detroit, MI 48202, USA. janagli1@hfhs.org
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood-Brain Barrier / metabolism
Brain / drug effects*,  physiopathology
Calcium-Binding Proteins / administration & dosage,  therapeutic use
Calpain / administration & dosage,  antagonists & inhibitors,  metabolism,  therapeutic use*
Cerebral Infarction / drug therapy*,  physiopathology
Cysteine Proteinase Inhibitors / administration & dosage,  metabolism,  therapeutic use*
Disease Models, Animal
Male
Peptide Fragments / administration & dosage,  metabolism,  therapeutic use*
Rats
Rats, Wistar
Spectrin / metabolism
Grant Support
ID/Acronym/Agency:
NS058581-01/NS/NINDS NIH HHS; R01 NS39075/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/B27-HYD peptide; 0/Calcium-Binding Proteins; 0/Cysteine Proteinase Inhibitors; 0/Peptide Fragments; 12634-43-4/Spectrin; 79079-11-1/calpastatin; EC 3.4.22.-/Calpain

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


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