PLAGL2 translocation and SP-C promoter activity-A cellular response of lung cells to hypoxia

Yuhong Guo, Meng Chun Yang, Jonathan C. Weissler, Yih Sheng Yang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Cobalt is a transition metal which can substitute for iron in the oxygen-sensitive protein and mimic hypoxia. Cobalt was known to be associated with the development of lung disease. In this study, when lung cells were exposed to hypoxia-induced by CoCl2 at a sub-lethal concentration (100 μM), their thyroid transcription factor-1 (TTF-1) expression was greatly reduced. Under this condition, SP-B promoter activity was down-regulated, but SP-C promoter remained active. Therefore, we hypothesized that other factor(s) besides TTF-1 might contribute to the modulation of SP-C promoter in hypoxic lung cells. Pleomorphic adenoma gene like-2 (PLAGL2), a previously identified TTF-1-independent activator of the SP-C promoter, was not down-regulated, nor increased, within those cells. Its cellular location was redistributed from the cytoplasm to the nucleus. Chromatin immunoprecipitation (ChIP) and quantitative RT-PCR analyses demonstrated that nuclear PLAGL2 occupied and transactivated the endogenous SP-C promoter in lung cells. Thereby, through relocating and accumulating of PLAGL2 inside the nucleus, PLAGL2 interacted with its target genes for various cellular functions. These results further suggest that PLAGL2 is an oxidative stress responding regulator in lung cells.

Original languageEnglish (US)
Pages (from-to)659-665
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume360
Issue number3
DOIs
StatePublished - Aug 31 2007

Keywords

  • Cobalt chloride
  • Differential regulation
  • Hypoxia
  • PLAGL2
  • Relocation
  • SP-B
  • SP-C
  • TTF-1
  • Translocation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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