Document Detail

Caveolin-1 regulates the secretion and cytoprotection of Cyr61 in hyperoxic cell death.
MedLine Citation:
PMID:  18801924     Owner:  NLM     Status:  MEDLINE    
Cysteine-rich 61 (Cyr61) belongs to the CCN family and mediates cell proliferation, survival, and apoptosis. Our previous studies showed that Cyr61 protected against hyperoxia-induced lung cell death via Akt phosphorylation. Caveolin-1 (cav-1), a 22-kDa transmembrane scaffolding protein, is the principal structural component of caveolae. Emerging data show that cav-1 regulates signal transduction-associated proteins that reside in the caveolae. Numerous integrin-related pathways, including PI3K/Akt-induced cell survival are controlled by cav-1-mediated signaling. Our data showed that recombinant Cyr61 promoted cell proliferation and resistance to hyperoxia-induced cell death in vitro. Neutralizing antibodies reversed the above effects, indicating functional role of secreted Cyr61 in response to hyperoxic stress. While deletion of cav-1 protected cells from hyperoxia-induced cell death, Cyr61-neutralizing antibodies abolished this protective effect. Furthermore, Cyr61 and cav-1 colocalized and physically interacted via integrins in bronchial epithelial cells. Deletion of cav-1 increased extracellular and decreased cytosolic Cyr61, both in vitro and in vivo. Pretreatment with Brefeldin A increased intracellular Cyr61 in cav-1(-/-) cells, while decreasing extracellular Cyr61. Taken together, Cav-1/Cyr61 interaction via integrins represents a novel pathway of Cyr61 signaling involving cav-1-dependent processes, which play a critical role in regulating hyperoxia-induced cell death.
Yang Jin; Hong Pyo Kim; Jiaofei Cao; Meng Zhang; Emeka Ifedigbo; Augustine M K Choi
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Publication Detail:
Type:  Journal Article     Date:  2008-09-18
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  23     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-30     Completed Date:  2009-02-16     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  341-50     Citation Subset:  IM    
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
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MeSH Terms
Antibodies / immunology,  pharmacology
Caveolin 1 / deficiency,  genetics,  metabolism*,  pharmacology*
Cell Death / drug effects
Cell Hypoxia / drug effects
Cell Proliferation
Cells, Cultured
Cysteine-Rich Protein 61 / immunology,  metabolism*,  secretion*
Cytoprotection / drug effects*
Gene Expression Regulation
Integrin alphaV / metabolism
Mice, Inbred C57BL
Mice, Knockout
Protein Binding
Reg. No./Substance:
0/Antibodies; 0/Caveolin 1; 0/Cysteine-Rich Protein 61; 0/Integrin alphaV

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