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 germfree GPX-DKO mice developed
severe acute colitis while their littermates with at least
one wildtype Gpx1 or Gpx2 gene remained virtually
symptomfree. 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 weekold 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 antiinflammatory activity.
Biological Chemistry keeps you up-to-date with the latest advances in the molecular life sciences. The journal publishes Research Articles, Short Communications, Reviews and Minireviews. Areas include: general biochemistry/pathobiochemistry, structural biology, molecular and cellular biology, genetics and epigenetics, virology, molecular medicine, plant molecular biology/biochemistry and novel experimental methodologies.