Caveolin-1 regulates the secretion and cytoprotection of Cyr61 in hyperoxic cell death. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antibodies
  • Cell Death
  • Cell Hypoxia
  • Cell Proliferation
  • Cells, Cultured
  • Exocytosis
  • Gene Expression Regulation
  • Integrin alphaV
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding

MeSH Major

  • Caveolin 1
  • Cysteine-Rich Protein 61
  • Cytoprotection

abstract

  • 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.

publication date

  • February 2009

has subject area

  • Animals
  • Antibodies
  • Caveolin 1
  • Cell Death
  • Cell Hypoxia
  • Cell Proliferation
  • Cells, Cultured
  • Cysteine-Rich Protein 61
  • Cytoprotection
  • Exocytosis
  • Gene Expression Regulation
  • Integrin alphaV
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1096/fj.08-108423

PubMed ID

  • 18801924

Additional Document Info

start page

  • 341

end page

  • 350

volume

  • 23

number

  • 2