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

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 (4 wk old male mice, n = 16 per group) were fed a standard diet (35 IU AT/kg diet) for 8–12 wk, exposed 6 h/day for 3 days to either to O₃ (0.5 ppm) 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 well-characterized mouse genes. As compared with filtered air exposure, O₃ 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 genes—Timp1, Areg, Birc5 and Tnc—were seen to be further modulated by AT status. The present study reveals AT modulation of adaptive response of lung genome to O₃ exposure.

Keywords::

• Alpha-tocopherol
• alpha-tocopherol transfer protein null mice
• gene expression profiling
• oxidative stress
• ozone
• vitamin E

Acknowledgments

Declaration of interest: This research was partly funded by grants from National Institute of Health Sciences (ES011895) and United States Department of Agriculture (35200-13456). The authors alone are responsible for the content and writing of the paper.