Hyperoxia-induced LC3B interacts with the Fas apoptotic pathway in epithelial cell death

Akihiko Tanaka, Yang Jin, Seon Jin Lee, Meng Zhang, Hong Pyo Kim, Donna B. Stolz, Stefan W. Ryter, Augustine M.K. Choi

Research output: Contribution to journalArticle

80 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)507-514
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume46
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • Apoptosis
  • Autophagy
  • Caveolin-1
  • Hyperoxia
  • Lung injury

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Hyperoxia-induced LC3B interacts with the Fas apoptotic pathway in epithelial cell death'. Together they form a unique fingerprint.

Cite this