Modulation of ozone-sensitive genes in alpha-tocopherol  transfer protein null mice.
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 O(3) (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 O(3) exposure. Lung genomic responses of the lungs to O(3) 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, 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 O(3)-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 O(3) 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 O(3) exposure.
Vasu
Vihas T
VT
Department of Internal Medicine, Center for Comparative Respiratory Biology and Medicine, Genome and Biomedical Sciences Facility, University of California, Davis, California 95616, USA. vtvasu@ucdavis.edu
Oommen
Saji
S
Lim
Yunsook
Y
Valacchi
Giuseppe
G
Hobson
Brad
B
Eirserich
Jason P
JP
Leonard
Scott W
SW
Traber
Maret G
MG
Cross
Carroll E
CE
Gohil
Kishorchandra
K
D000222:Adaptation, Physiological / Q000187:drug effects* / Q000235:genetics; D066258:Amphiregulin; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D004260:DNA Repair / Q000235:genetics; D066255:EGF Family of Proteins; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D019570:Inhalation Exposure; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000633:toxicity*; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D024502:alpha-Tocopherol / Q000378:metabolism*
D066258:Amphiregulin; C587849:Areg protein, mouse; C117749:Birc5 protein, mouse; D002352:Carrier Proteins; D066255:EGF Family of Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D051034:Inhibitor of Apoptosis Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010083:Oxidants, Photochemical; D012097:Repressor Proteins; D000077022:Survivin; D019715:Tissue Inhibitor of Metalloproteinase-1; C017763:alpha-tocopherol transfer protein; D010126:Ozone; D024502:alpha-Tocopherol