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 journalArticle

13 Citations (Scopus)

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

Fingerprint

Cell Hypoxia
Pleomorphic Adenoma
Genes
Lung
Cobalt
Pulmonary diseases
Oxidative stress
Chromatin Immunoprecipitation
Lung Diseases
Chromatin
Transition metals
Cytoplasm
Oxidative Stress
Iron
Metals
Modulation
Oxygen
Polymerase Chain Reaction
thyroid nuclear factor 1
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

PLAGL2 translocation and SP-C promoter activity-A cellular response of lung cells to hypoxia. / Guo, Yuhong; Yang, Meng Chun; Weissler, Jonathan C.; Yang, Yih Sheng.

In: Biochemical and Biophysical Research Communications, Vol. 360, No. 3, 31.08.2007, p. 659-665.

Research output: Contribution to journalArticle

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