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Vanadium-induced STAT-1 activation in lung myofibroblasts requires H2O2 and P38 MAP kinase.

Publication ,  Journal Article
Wang, Y-Z; Ingram, JL; Walters, DM; Rice, AB; Santos, JH; Van Houten, B; Bonner, JC
Published in: Free Radic Biol Med
October 15, 2003

Vanadium compounds present in air pollution particulate matter activate signal transduction pathways in pulmonary cell types leading to pathological outcomes including aberrant cell proliferation, apoptosis, and cytokine expression. Vanadium has been proposed to activate transcription factors via the generation of hydrogen peroxide (H2O2). We investigated the mechanisms through which vanadium pentoxide (V2O5), the major form of vanadium released from the industrial burning of fuel oil, activated the signal transducer and activator of transcription (STAT)-1. V2O5-induced STAT-1 activation was blocked by catalase and N-acetyl-L-cysteine (NAC), suggesting vanadium-induced generation of H2O2. Surprisingly, however, V2O5 did not increase H2O2 levels released by rat lung myofibroblasts into cell culture supernatants. Instead, these quiescent myofibroblasts spontaneously released micromolar concentrations of H2O2, and the addition of V2O5 reduced H2O2 levels in cell culture supernatants within minutes. V2O5 suppressed H2O2 for as long as 24 h. Differences in the temporal activation of STAT-1 and p38 MAPK were observed following V2O5 or H2O2 treatment, and STAT-1 activation by V2O5 or H2O2 was attenuated by an inhibitor of the EGF receptor tyrosine kinase (AG1478) or p38 MAPK (SB203580). The phosphorylation of p38 MAPK by V2O5 was inhibited by NAC and catalase, yet the EGF receptor inhibitor AG1478 had no effect on V2O5-induced p38 MAPK activation. Collectively, our findings support the novel hypothesis that H2O2 spontaneously generated by myofibroblasts fuels vanadium-induced activation of STAT-1. Moreover, p38 MAPK and EGF receptor activation are required for V2O5-induced STAT-1 activation.

Duke Scholars

Published In

Free Radic Biol Med

DOI

ISSN

0891-5849

Publication Date

October 15, 2003

Volume

35

Issue

8

Start / End Page

845 / 855

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Vanadium Compounds
  • Trans-Activators
  • STAT1 Transcription Factor
  • Rats
  • Phosphorylation
  • Mitogen-Activated Protein Kinases
  • Lung
  • Hydrogen Peroxide
  • Fibroblasts
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, Y.-Z., Ingram, J. L., Walters, D. M., Rice, A. B., Santos, J. H., Van Houten, B., & Bonner, J. C. (2003). Vanadium-induced STAT-1 activation in lung myofibroblasts requires H2O2 and P38 MAP kinase. Free Radic Biol Med, 35(8), 845–855. https://doi.org/10.1016/s0891-5849(03)00399-x
Wang, Yi-Zhe, Jennifer L. Ingram, Dianne M. Walters, Annette B. Rice, Janine H. Santos, Bennett Van Houten, and James C. Bonner. “Vanadium-induced STAT-1 activation in lung myofibroblasts requires H2O2 and P38 MAP kinase.Free Radic Biol Med 35, no. 8 (October 15, 2003): 845–55. https://doi.org/10.1016/s0891-5849(03)00399-x.
Wang Y-Z, Ingram JL, Walters DM, Rice AB, Santos JH, Van Houten B, et al. Vanadium-induced STAT-1 activation in lung myofibroblasts requires H2O2 and P38 MAP kinase. Free Radic Biol Med. 2003 Oct 15;35(8):845–55.
Wang, Yi-Zhe, et al. “Vanadium-induced STAT-1 activation in lung myofibroblasts requires H2O2 and P38 MAP kinase.Free Radic Biol Med, vol. 35, no. 8, Oct. 2003, pp. 845–55. Pubmed, doi:10.1016/s0891-5849(03)00399-x.
Wang Y-Z, Ingram JL, Walters DM, Rice AB, Santos JH, Van Houten B, Bonner JC. Vanadium-induced STAT-1 activation in lung myofibroblasts requires H2O2 and P38 MAP kinase. Free Radic Biol Med. 2003 Oct 15;35(8):845–855.
Journal cover image

Published In

Free Radic Biol Med

DOI

ISSN

0891-5849

Publication Date

October 15, 2003

Volume

35

Issue

8

Start / End Page

845 / 855

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Vanadium Compounds
  • Trans-Activators
  • STAT1 Transcription Factor
  • Rats
  • Phosphorylation
  • Mitogen-Activated Protein Kinases
  • Lung
  • Hydrogen Peroxide
  • Fibroblasts