Modulation of ozone-sensitive genes in alpha-tocopherol transfer protein null mice

Vihas T. Vasu, Saji Oommen, Yunsook Lim, Giuseppe Valacchi, Brad Hobson, Jason P. Eiserich, Scott W. Leonard, Maret G. Traber, Carroll E Cross, Kishorchandra Gohil

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Alpha-tocopherol transfer protein (ATTP) null mice (ATTP-/-) have a systemic alpha-tocopherol (AT) deficiency, with their lung AT levels being <10% of those in AT-replete ATTP/ mice when fed a standard rodent chow diet. ATTP/ and ATTP-/- mice (4wk old male mice, n16 per group) were fed a standard diet (35 IU AT/kg diet) for 812wk, exposed 6h/day for 3 days to either to O3 (0.5ppm) or filtered air, then sacrificed. No significant differences in plasma or lung AT concentrations were observed in response to this level of O3 exposure. Lung genomic responses of the lungs to O3 were determined using Affymetrix 430A 2.0 arrays containing over 22,600 probe sets representing 14,000 ell-characterized mouse genes. As compared with filtered air exposure, O 3 exposure resulted in 99 genes being differentially expressed in ATTP-/- mice, as compared to 52 differentially expressed genes in ATTP/ mice. The data revealed an O3-induced upregulation of genes related to cell proliferation/DNA repair and inflammatory-immune responses in both ATTP/ and ATTP-/- mice, with the expression of 22 genes being common to both, whereas 30 and 77 genes were unique to ATTP/ and ATTP-/- mice, respectively. The expressions of O3 sensitive genesTimp1, Areg, Birc5 and Tncwere seen to be further modulated by AT status. The present study reveals AT modulation of adaptive response of lung genome to O3 exposure.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalInhalation Toxicology
Volume22
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Alpha-tocopherol
  • Alpha-tocopherol transfer protein null mice
  • Gene expression profiling
  • Oxidative stress
  • Ozone
  • Vitamin E

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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    Vasu, V. T., Oommen, S., Lim, Y., Valacchi, G., Hobson, B., Eiserich, J. P., Leonard, S. W., Traber, M. G., Cross, C. E., & Gohil, K. (2010). Modulation of ozone-sensitive genes in alpha-tocopherol transfer protein null mice. Inhalation Toxicology, 22(1), 1-16. https://doi.org/10.3109/08958370902838145