Document Detail


Localization and characterization of N-ethylmaleimide sensitive inhibitor(s) of thiol cathepsin activity from cultured nil and polyoma virus-transformed nil hamster cells.
MedLine Citation:
PMID:  6267078     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exposure of cultured Nil (a stable line of fibroblast cells from Syrian hamsters) or polyoma virus-transformed (PyNil) hamster fibroblasts to 0.5 mM N-ethylmaleimide for 5 minutes resulted in striking increases in thiol cathepsin activity in unfractionated cell-free lysates. The paradoxical increase in activity of the normally N-ethylmaleimide-sensitive cathepsins apparently occurred as the result of the protective compartmentalization of the cathepsins in the lysosomes (20,000 X g sedimented fraction) and the unprotected localization of an inhibitor(s) in the soluble cytoplasm (175,000 X g supernatant fraction). Under continuous exposure of the cells to N-ethylmaleimide, a rapid increase in cathepsin activity (seen in the first 5 minutes) was followed by a steady decrease in activity (half inactivation time, 90 minutes). The relative difference in rates of N-ethylmaleimide inactivation of thiol cathepsins and thiol cathepsin inhibitors provides a means for estimating lysosomal cathepsin activity in whole cell extracts without the need for more time-consuming fractionation procedure. In reciprocal inhibition tests, it was found that, regardless of the source of cathepsins, the Nil and PyNil cathepsin inhibitor(s) inactivated the cathepsins to approximately the same extent. The inhibitors were heat stable (90-100 degrees C for 15 minutes) at pH 4, but were totally inactivated when boiled at pH 8.5. On a calibrated Sephadex G-100 column, the relative molecular weight (Mr) of the inhibitor(s) was 13,000 daltons. On the same column, the Mr of the cathepsins was 24,000 daltons. Compared with the cathepsin activity from Nil cells, there was about five times less cathepsin activity recoverable from the PyNil cells.
Authors:
R A Morgan; K L Inge; C W Christopher
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  108     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  1981 Jul 
Date Detail:
Created Date:  1981-10-25     Completed Date:  1981-10-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  55-66     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aminopeptidases / antagonists & inhibitors
Animals
Benzoylarginine-2-Naphthylamide / antagonists & inhibitors
Cathepsin H
Cathepsins / antagonists & inhibitors*,  metabolism
Cell Compartmentation
Cell Fractionation
Cell Line
Cell Transformation, Viral
Cricetinae
Cysteine Endopeptidases*
Cytoplasm / analysis*
Ethylmaleimide / pharmacology*
Hydrogen-Ion Concentration
Lysosomes / enzymology*
Molecular Weight
Polyomavirus
Temperature
Grant Support
ID/Acronym/Agency:
GM 27905/GM/NIGMS NIH HHS; RR 07043/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
128-53-0/Ethylmaleimide; 305-09-9/Benzoylarginine-2-Naphthylamide; EC 3.4.-/Cathepsins; EC 3.4.11.-/Aminopeptidases; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.22.16/Cathepsin H

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


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