Document Detail


Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation.
MedLine Citation:
PMID:  11245599     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The potential role of caveolin-1 in apoptosis remains controversial. Here, we investigate whether caveolin-1 expression is proapoptotic or antiapoptotic using a well-defined antisense approach. We show that NIH/3T3 cells harboring antisense caveolin-1 are resistant to staurosporine-induced apoptosis, as assessed using cell morphology, DNA content, caspase 3 activation, and focal adhesion kinase cleavage. Importantly, sensitivity to apoptosis is recovered when caveolin-1 levels are restored. Conversely, recombinant stable expression of caveolin-1 in T24 bladder carcinoma cells sensitizes these cells to caspase 3 activation. Consistent with the observations using NIH/3T3 cells, downregulation of caveolin-1 in T24 cells substantially diminishes caspase 3-like activity. Loss of sensitivity to apoptotic stimulation is recovered by inhibition of the phosphatidylinositol 3-kinase pathway using LY-294002, suggesting a possible mechanism for the sensitizing effect of caveolin-1. Thus our results suggest that caveolin-1 may act as a coupling or sensitizing factor in signaling apoptotic cell death in both fibroblastic (NIH/3T3) and epithelial (T24) cells.
Authors:
J Liu; P Lee; F Galbiati; R N Kitsis; M P Lisanti
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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:  American journal of physiology. Cell physiology     Volume:  280     ISSN:  0363-6143     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-03-14     Completed Date:  2001-04-12     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C823-35     Citation Subset:  IM    
Affiliation:
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
Apoptosis / drug effects,  physiology*
Caspase 3
Caspases / metabolism
Caveolin 1
Caveolins / genetics*
Chromones / pharmacology
DNA, Antisense
Down-Regulation / physiology
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Epithelial Cells / cytology*,  enzymology
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Gene Expression / physiology
Humans
MAP Kinase Signaling System / drug effects,  physiology*
Mice
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / metabolism
Morpholines / pharmacology
Phosphatidylinositol 3-Kinases / metabolism
Protein-Tyrosine Kinases / metabolism
Staurosporine / pharmacology
Tumor Cells, Cultured / cytology,  enzymology
Urinary Bladder Neoplasms
Grant Support
ID/Acronym/Agency:
R01-HL-60665/HL/NHLBI NIH HHS; R01-HL-61550/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/CAV1 protein, human; 0/Cav1 protein, mouse; 0/Caveolin 1; 0/Caveolins; 0/Chromones; 0/DNA, Antisense; 0/Enzyme Inhibitors; 0/Morpholines; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 62996-74-1/Staurosporine; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Focal Adhesion Kinase 1; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.2/Focal Adhesion Protein-Tyrosine Kinases; EC 2.7.10.2/PTK2 protein, human; EC 2.7.10.2/Ptk2 protein, mouse; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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