Document Detail


Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons. Implications for the regulation of motor learning and neuronal survival.
MedLine Citation:
PMID:  9407089     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A cDNA clone for the serine proteinase inhibitor (serpin), neuroserpin, was isolated from a human whole brain cDNA library, and recombinant protein was expressed in insect cells. The purified protein is an efficient inhibitor of tissue type plasminogen activator (tPA), having an apparent second-order rate constant of 6. 2 x 10(5) M-1 s-1 for the two-chain form. However, unlike other known plasminogen activator inhibitors, neuroserpin is a more effective inactivator of tPA than of urokinase-type plasminogen activator. Neuroserpin also effectively inhibited trypsin and nerve growth factor-gamma but reacted only slowly with plasmin and thrombin. Northern blot analysis showed a 1.8 kilobase messenger RNA expressed predominantly in adult human brain and spinal cord, and immunohistochemical studies of normal mouse tissue detected strong staining primarily in neuronal cells with occasionally positive microglial cells. Staining was most prominent in the ependymal cells of the choroid plexus, Purkinje cells of the cerebellum, select neurons of the hypothalamus and hippocampus, and in the myelinated axons of the commissura. Expression of tPA within these regions is reported to be high and has previously been correlated with both motor learning and neuronal survival. Taken together, these data suggest that neuroserpin is likely to be a critical regulator of tPA activity in the central nervous system, and as such may play an important role in neuronal plasticity and/or maintenance.
Authors:
G A Hastings; T A Coleman; C C Haudenschild; S Stefansson; E P Smith; R Barthlow; S Cherry; M Sandkvist; D A Lawrence
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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:  The Journal of biological chemistry     Volume:  272     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-01-23     Completed Date:  1998-01-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  33062-7     Citation Subset:  IM    
Affiliation:
Department of Protein Therapeutics, Human Genome Sciences Inc., Rockville, Maryland 20850, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / cytology
Brain Chemistry*
Cell Survival
Glycoproteins / chemistry*
Humans
Immunoenzyme Techniques
Kinetics
Mice
Neurons / chemistry,  cytology*
Neuropeptides / chemistry*,  metabolism
RNA, Messenger / analysis
Serine Proteinase Inhibitors / chemistry*
Serpins / chemistry*,  metabolism
Spodoptera
Tissue Distribution
Tissue Plasminogen Activator / antagonists & inhibitors*
Grant Support
ID/Acronym/Agency:
HL 55374/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Glycoproteins; 0/Neuropeptides; 0/RNA, Messenger; 0/Serine Proteinase Inhibitors; 0/Serpins; 0/neuroserpin; EC 3.4.21.68/Tissue Plasminogen Activator

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


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