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Caveolin-1 mediates Fas-BID signaling in hyperoxia-induced apoptosis

Meng Zhang1, Seon-Jin Lee, ChangHyeok An

  • 1Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Free Radical Biology & Medicine
|March 9, 2011
PubMed

Insights

Caveolin-1 (Cav-1) regulates hyperoxia-induced apoptosis by interacting with Fas and BID, bridging extrinsic and intrinsic cell death pathways. Cav-1 is essential for death-inducing signaling complex (DISC) formation and subsequent cell death.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Apoptosis Signaling

Background:

  • Fas-mediated apoptosis is a critical cellular process involving the death-inducing signaling complex (DISC).
  • The precise mechanisms governing DISC component aggregation and activation remain incompletely understood.
  • Cav-1's role in regulating Fas signaling and linking extrinsic and intrinsic apoptosis pathways has not been fully elucidated.

Purpose of the Study:

  • To investigate the role of Caveolin-1 (Cav-1) in hyperoxia-induced apoptosis.
  • To elucidate the molecular mechanisms by which Cav-1 regulates Fas signaling and mediates communication between extrinsic and intrinsic apoptotic pathways.
  • To determine the interaction of Cav-1 with Fas and BID in the context of reactive oxygen species (ROS).

Main Methods:

  • Utilized hyperoxia exposure to induce apoptosis in cellular models.
  • Investigated the colocalization and interaction of Cav-1 with Fas and BID using biochemical assays.
  • Employed Cav-1 knockout (Cav-1-/-) and mutant (Y14F) models to assess functional consequences.
  • Assessed the impact of ROS scavengers (N-acetylcysteine) and siRNA-mediated gene silencing (glutathione peroxidase-2) on apoptosis signaling.

Main Results:

  • Hyperoxia increased Cav-1 and Fas colocalization and interaction, preceding DISC formation.
  • Cav-1 deletion disrupted DISC formation, while Cav-1 interacted with BID.
  • Cav-1 Y14F mutation impaired BID-Cav-1 interaction, reducing truncated BID (tBID) levels and conferring resistance to hyperoxia-induced apoptosis.
  • ROS modulated Cav-1-Fas interaction, and glutathione peroxidase-2 influenced BID-Cav-1 interaction and tBID formation.

Conclusions:

  • Cav-1 plays a crucial role in regulating hyperoxia/ROS-induced apoptosis.
  • Cav-1 acts as a mediator between extrinsic (Fas/DISC) and intrinsic (mitochondrial) apoptotic pathways.
  • Cav-1 interacts with both Fas and BID, likely through Fas palmitoylation and Cav-1 Y14 phosphorylation, to facilitate apoptosis.

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