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Microflora trigger colitis in mice deficient in selenium-dependent glutathione peroxidase and induce Gpx2 gene expression.
Biol Chem 2003; 384(4):597-607BC

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.

Authors+Show Affiliations

Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12751789

Citation

Esworthy, R Steven, et al. "Microflora Trigger Colitis in Mice Deficient in Selenium-dependent Glutathione Peroxidase and Induce Gpx2 Gene Expression." Biological Chemistry, vol. 384, no. 4, 2003, pp. 597-607.
Esworthy RS, Binder SW, Doroshow JH, et al. Microflora trigger colitis in mice deficient in selenium-dependent glutathione peroxidase and induce Gpx2 gene expression. Biol Chem. 2003;384(4):597-607.
Esworthy, R. S., Binder, S. W., Doroshow, J. H., & Chu, F. F. (2003). Microflora trigger colitis in mice deficient in selenium-dependent glutathione peroxidase and induce Gpx2 gene expression. Biological Chemistry, 384(4), pp. 597-607.
Esworthy RS, et al. Microflora Trigger Colitis in Mice Deficient in Selenium-dependent Glutathione Peroxidase and Induce Gpx2 Gene Expression. Biol Chem. 2003;384(4):597-607. PubMed PMID: 12751789.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microflora trigger colitis in mice deficient in selenium-dependent glutathione peroxidase and induce Gpx2 gene expression. AU - Esworthy,R Steven, AU - Binder,Scott W, AU - Doroshow,James H, AU - Chu,Fong-Fong, PY - 2003/5/20/pubmed PY - 2003/12/5/medline PY - 2003/5/20/entrez SP - 597 EP - 607 JF - Biological chemistry JO - Biol. Chem. VL - 384 IS - 4 N2 - 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. SN - 1431-6730 UR - https://www.unboundmedicine.com/medline/citation/12751789/Microflora_trigger_colitis_in_mice_deficient_in_selenium_dependent_glutathione_peroxidase_and_induce_Gpx2_gene_expression_ L2 - https://www.degruyter.com/doi/10.1515/BC.2003.067 DB - PRIME DP - Unbound Medicine ER -