Document Detail


A new mechanism for prolactin processing into 16K PRL by secreted cathepsin D.
MedLine Citation:
PMID:  16959874     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cathepsins are lysosomal enzymes that were shown to release the antiangiogenic fragments 16K prolactin (PRL), endostatin, and angiostatin by processing precursors at acidic pH in vitro. However, the physiological relevance of these findings is questionable because the neutral pH of physiological fluids is not compatible with the acidic conditions required for the proteolytic activity of these enzymes. Here we show that cathepsin D secreted from various tissues is able to process PRL into 16K PRL outside the cell. To specifically target extracellular proteolysis, we used tissues from PRL receptor-deficient mice, which are unable to internalize PRL. As assessed by the use of specific inhibitors of proton extruders, we show that the proteolytic activity of cathepsin D requires local acid secretion driven by Na(+)/H(+) exchangers and H(+)/ATPase. Although it is usually assumed that cathepsin-mediated generation of antiangiogenic peptides occurs in the moderately acidic pericellular milieu found in malignant tumors, we propose a new mechanism explaining the extracellular activity of this acidic protease under physiological pH. Our data support the concept that secreted lysosomal enzymes could be involved in the maintenance of angiogenesis dormancy via the generation of active antiangiogenic peptides in nonpathological contexts.
Authors:
David Piwnica; Isabelle Fernandez; Nadine Binart; Philippe Touraine; Paul A Kelly; Vincent Goffin
Related Documents :
1647534 - Phaclofen-sensitive gaba-b receptors do not mediate excitatory effects of baclofen on g...
7485014 - Modulatory impact of acid and pepsin on esophageal hydrophobicity in humans.
192884 - Metiamide and stimulated acid secretion from the isolated non-distended and distended m...
9192644 - Defensive production of formic acid (80%) by a carabid beetle (galerita lecontei).
15153034 - A concise asymmetric synthesis of (2s,3s,7s)-3,7-dimethylpentadecan-2-yl acetate and pr...
12139444 - Mixed steroidal 1,2,4,5-tetraoxanes: antimalarial and antimycobacterial activity.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-07
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  20     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-28     Completed Date:  2007-02-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3263-78     Citation Subset:  IM    
Affiliation:
Institut National de la Santé et de la Recherche Médicale, (INSERM), Unité (U) 808, F-75730 Paris Cedex 15, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cathepsin D / metabolism,  secretion*
Cells, Cultured
Culture Media, Conditioned
Hydrogen-Ion Concentration
Lysosomes / enzymology*
Mice
Mice, Knockout
Models, Biological
Mutation
Prolactin / metabolism*
Proton-Translocating ATPases / antagonists & inhibitors,  metabolism*
Receptors, Prolactin / genetics,  metabolism*
Sodium-Hydrogen Antiporter / antagonists & inhibitors,  metabolism*
Tissue Distribution
Chemical
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Receptors, Prolactin; 0/Sodium-Hydrogen Antiporter; 9002-62-4/Prolactin; EC 3.4.23.5/Cathepsin D; EC 3.6.3.14/Proton-Translocating ATPases

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


Previous Document:  Human homologs of the putative G protein-coupled membrane progestin receptors (mPRalpha, beta, and g...
Next Document:  The role of interleukin-11 in pregnancy involves up-regulation of alpha2-macroglobulin gene through ...