Document Detail

Yessotoxin inhibits the complete degradation of E-cadherin.
MedLine Citation:
PMID:  18155346     Owner:  NLM     Status:  MEDLINE    
Previous in vitro and in vivo toxicological studies on the effects of yessotoxin (YTX) on E-cadherin have provided conflicting results with regard to alterations of its turnover. We have then studied the effects of YTX on the degradation pathway of E-cadherin in intact cells under controlled conditions, and found that the 100kDa E-cadherin fragment (ECRA100) accumulated in cells exposed to YTX is an intermediate degradation product, detectable when the process is altered by agents interfering with endocytosis and lysosomal functioning. Cell treatment with YTX slows down the degradation of ECRA100, without affecting the half-lives of intact E-cadherin and its associated proteins beta-catenin and gamma-catenin. When cells have been treated with an inhibitor of proteasomes (lactacystin), the accumulation of ECRA100 induced by YTX was reduced. Accumulation of ECRA100, in turn, was observed after cells were exposed to inhibitors of lysosomal functioning (chloroquine) and of clathrin-mediated endocytosis (chloropromazine), but not to agents interfering with the caveolae-mediated pathway (nystatin and filipin III). The actin cytoskeleton was involved in endocytosis of ECRA100, because its accumulation was detected after MCF-7 cells had been treated with cytochalasin D. Nocodazole treatment of MCF-7 cells, in turn, did not lead to detection of ECRA100, indicating that microtubules should not be involved in its degradation. We have concluded that YTX interferes with the degradation pathway of E-cadherin by slowing down the endocytosis and complete disposal of the ECRA100 intermediate proteolytic fragment, whose cell levels are consequently increased in cells exposed to the toxin. These findings reconcile the apparent contradictions of previous studies, showing that YTX does not promote E-cadherin degradation per se, but interferes with its complete disposal.
Federica Callegari; Gian Paolo Rossini
Related Documents :
12851396 - Biological activities and pore formation of clostridium perfringens beta toxin in hl 60...
12165316 - Clostridium botulinum c2 toxin: binding studies with fluorescence-activated cytometry.
9647696 - Histopathological effects of bacillus thuringiensis on the alimentary canal of the shee...
3744556 - Early events in the action of staphylococcal alpha-toxin on the plasma membrane of adre...
12513856 - Fertilization of mouse oocytes using somatic cells as male germ cells.
3968176 - Assembled and unassembled pools of clathrin: a quantitative study using an enzyme immun...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-11-21
Journal Detail:
Title:  Toxicology     Volume:  244     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-03-03     Completed Date:  2008-04-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  133-44     Citation Subset:  IM    
Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Via G. Campi 287, I-41100 Modena, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Acetylcysteine / analogs & derivatives,  pharmacology
Cadherins / metabolism*
Cell Adhesion / drug effects
Cell Line, Tumor
Cysteine Proteinase Inhibitors / pharmacology
DNA / analysis,  biosynthesis
Electrophoresis, Polyacrylamide Gel
Endocytosis / drug effects
Ethers, Cyclic / pharmacology*
Membrane Proteins / metabolism
Mollusk Venoms / pharmacology*
Oxocins / pharmacology*
Trypsin / chemistry
Reg. No./Substance:
0/Cadherins; 0/Cysteine Proteinase Inhibitors; 0/Ethers, Cyclic; 0/Membrane Proteins; 0/Mollusk Venoms; 0/Oxocins; 112514-54-2/yessotoxin; 133343-34-7/lactacystin; 616-91-1/Acetylcysteine; 9007-49-2/DNA; EC

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

Previous Document:  Yessotoxin induces the accumulation of altered E-cadherin dimers that are not part of adhesive struc...
Next Document:  Characterization of chlorpyrifos-induced apoptosis in placental cells.