Hyperoxia-induced LC3B interacts with the Fas apoptotic pathway in epithelial cell death. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antigens, CD95
  • Autophagy
  • Biological Markers
  • Bronchi
  • Caspase 8
  • Caveolin 1
  • Cell Death
  • Cells, Cultured
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering
  • Tyrosine

MeSH Major

  • Apoptosis
  • Epithelial Cells
  • Hyperoxia
  • Microtubule-Associated Proteins

abstract

  • Epithelial cell death plays a critical role in hyperoxia-induced lung injury. We investigated the involvement of the autophagic marker microtubule-associated protein-1 light chain-3B (LC3B) in epithelial cell apoptosis after hyperoxia. Prolonged hyperoxia (>95% O(2)), which causes characteristic lung injury in mice, activated morphological and biochemical markers of autophagy. Hyperoxia induced the time-dependent expression and conversion of LC3B-I to LC3B-II in mouse lung in vivo and in cultured epithelial cells (Beas-2B, human bronchial epithelial cells) in vitro. Hyperoxia increased autophagosome formation in Beas-2B cells, as evidenced by electron microscopy and increased GFP-LC3 puncta. The augmented LC3B level after hyperoxia was transcriptionally regulated and dependent in part on the c-Jun N-terminal kinase pathway. We hypothesized that LC3B plays a regulatory role in hyperoxia-induced epithelial apoptosis. LC3B siRNA promoted hyperoxia-induced cell death in epithelial cells, whereas overexpression of LC3B conferred cytoprotection after hyperoxia. The autophagic protein LC3B cross-regulated the Fas apoptotic pathway by physically interacting with the components of death-inducing signaling complex. This interaction was mediated by caveolin-1 tyrosine 14, which is a known target of phosphorylation induced by hyperoxia. Taken together, hyperoxia-induced LC3B activation regulates the Fas apoptotic pathway and thus confers cytoprotection in lung epithelial cells. The interaction of LC3B and Fas pathways requires cav-1.

publication date

  • April 2012

has subject area

  • Animals
  • Antigens, CD95
  • Apoptosis
  • Autophagy
  • Biological Markers
  • Bronchi
  • Caspase 8
  • Caveolin 1
  • Cell Death
  • Cells, Cultured
  • Epithelial Cells
  • Humans
  • Hyperoxia
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Tyrosine

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3359946

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2009-0415OC

PubMed ID

  • 22095627

Additional Document Info

start page

  • 507

end page

  • 514

volume

  • 46

number

  • 4