TY - JOUR
T1 - Caveolin-1 regulates the secretion and cytoprotection of Cyr61 in hyperoxic cell death
AU - Jin, Yang
AU - Kim, Hong Pyo
AU - Cao, Jiaofei
AU - Zhang, Meng
AU - Ifedigbo, Emeka
AU - Choi, Augustine M.K.
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/2
Y1 - 2009/2
N2 - Cysteine-rich 61 (cyr61) belongs to the ccn family and mediates cell roliferationsurvival, and apoptosis. Ourprevious 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-mediatedsignaling. Our data showed that recombinant cyr61 promoted cell proliferation and resistance to hyperoxia-inducedcell death in vitro. Neutralizing antibodies reversed the above effects, indicating functional role of secreted cyr61 inresponse 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 cytosoliccyr61, 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 pathwayof cyr61 signaling involving cav-1-dependent processes, which play a critical role in regulating hyperoxia-induced celldeath.
AB - Cysteine-rich 61 (cyr61) belongs to the ccn family and mediates cell roliferationsurvival, and apoptosis. Ourprevious 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-mediatedsignaling. Our data showed that recombinant cyr61 promoted cell proliferation and resistance to hyperoxia-inducedcell death in vitro. Neutralizing antibodies reversed the above effects, indicating functional role of secreted cyr61 inresponse 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 cytosoliccyr61, 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 pathwayof cyr61 signaling involving cav-1-dependent processes, which play a critical role in regulating hyperoxia-induced celldeath.
KW - CNN
KW - Exocytosis
KW - Signaling
UR - http://www.scopus.com/inward/record.url?scp=59649124305&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59649124305&partnerID=8YFLogxK
U2 - 10.1096/fj.08-108423
DO - 10.1096/fj.08-108423
M3 - Article
C2 - 18801924
AN - SCOPUS:59649124305
SN - 0892-6638
VL - 23
SP - 341
EP - 350
JO - FASEB Journal
JF - FASEB Journal
IS - 2
ER -