Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced apoptosis. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cells, Cultured
  • Epithelial Cells
  • Humans
  • Lung
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout

MeSH Major

  • Antigens, CD95
  • Apoptosis
  • BH3 Interacting Domain Death Agonist Protein
  • Caveolin 1
  • Hyperoxia
  • Signal Transduction

abstract

  • Fas-mediated apoptosis is a crucial cellular event. Fas, the Fas-associated death domain, and caspase 8 form the death-inducing signaling complex (DISC). Activated caspase 8 mediates the extrinsic pathways and cleaves cytosolic BID. Truncated BID (tBID) translocates to the mitochondria, facilitates the release of cytochrome c, and activates the intrinsic pathways. However, the mechanism causing these DISC components to aggregate and form the complex remains unclear. We found that Cav-1 regulated Fas signaling and mediated the communication between extrinsic and intrinsic pathways. Shortly after hyperoxia (4 h), the colocalization and interaction of Cav-1 and Fas increased, followed by Fas multimer and DISC formation. Deletion of Cav-1 (Cav-1-/-) disrupted DISC formation. Further, Cav-1 interacted with BID. Mutation of Cav-1 Y14 tyrosine to phenylalanine (Y14F) disrupted the hyperoxia-induced interaction between BID and Cav-1 and subsequently yielded a decreased level of tBID and resistance to hyperoxia-induced apoptosis. The reactive oxygen species (ROS) scavenger N-acetylcysteine decreased the Cav-1-Fas interaction. Deletion of glutathione peroxidase-2 using siRNA aggravated the BID-Cav-1 interaction and tBID formation. Taken together, these results indicate that Cav-1 regulates hyperoxia/ROS-induced apoptosis through interactions with Fas and BID, probably via Fas palmitoylation and Cav-1 Y14 phosphorylation, respectively. Copyright © 2011 Elsevier Inc. All rights reserved.

publication date

  • May 15, 2011

has subject area

  • Animals
  • Antigens, CD95
  • Apoptosis
  • BH3 Interacting Domain Death Agonist Protein
  • Caveolin 1
  • Cells, Cultured
  • Epithelial Cells
  • Humans
  • Hyperoxia
  • Lung
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4134776

Digital Object Identifier (DOI)

  • 10.1016/j.freeradbiomed.2011.02.031

PubMed ID

  • 21382479

Additional Document Info

start page

  • 1252

end page

  • 1262

volume

  • 50

number

  • 10