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PMID:12751789
| Citation |
Esworthy, RS, Binder, SW, Doroshow, JH and Chu, FF (2003) Microflora trigger colitis in mice deficient in selenium-dependent glutathione peroxidase and induce Gpx2 gene expression. Biol. Chem. 384:597-607 |
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| Abstract |
Selenium-dependent glutathione peroxidase isoenzymes-1 and -2 are the major glutathione-dependent H2O2-reducing activities in the epithelium of the mid- to lower gastrointestinal tract. The two isoenzymes protect mice against ileocolitis. We have found that luminal microflora are required for colitis to develop in mice deficient in GPX-1 and GPX-2 activity (GPX-DKO). Within 7 days of association with microflora, previously asymptomatic germ-free GPX-DKO mice developed severe acute colitis while their littermates with at least one wild-type Gpx1 or Gpx2 gene remained virtually symptom-free. Microflora also affected Gpx2 gene expression. Gpx2, but not Gpx1, mRNA levels were elevated 4-5 fold in the ileum and colon in conventionally reared or microflora-associated adult mice compared with germ-free mice. Since the gastrointestinal tract microflora undergo major changes 2-3 weeks after birth, from relatively benign to a potentially stressful composition, we examined postnatal Gpx2 gene expression. The jejunal and ileal GPX-2 activity levels were low in two to three week-old mice and increased 5-7 fold during the next two weeks. GPX-2 activity levels were correlated with the mRNA levels. Colon Gpx2 mRNA levels held steady at about 50% of adult levels from 12-21 days of age but were several times higher than ileal levels. Our results suggest that ileal Gpx2 mRNA and GPX-2 activity levels are induced by luminal microflora. This response is consistent with a role for GPX as an anti-inflammatory activity. |
| Links |
PubMed Online version:10.1515/BC.2003.067 |
| Keywords |
Aging/physiology; Animals; Antibodies/analysis; Colitis/enzymology; Colitis/microbiology; Colitis/pathology; Colon/microbiology; Colon/pathology; Gene Expression Regulation, Enzymologic/physiology; Germ-Free Life; Glutathione Peroxidase/biosynthesis; Glutathione Peroxidase/deficiency; Glutathione Peroxidase/genetics; Ileum/growth & development; Ileum/microbiology; Ileum/pathology; Immunohistochemistry; Mice; Mice, Knockout; RNA, Messenger/biosynthesis; RNA, Messenger/genetics; Selenium/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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