Low glutathione peroxidase activity in Gpx1 knockout mice protects jejunum crypts from g-irradiation damage

Esworthy, R. Steven, Jeffrey R. Mann, Mindy Sam, and Fong-Fong Chu. Low glutathione peroxidase activity in Gpx1 knockout mice protects jejunum crypts from g-irradiation damage. Am J Physiol Gastrointest Liver Physiol 279: G426–G436, 2000.—Gpx1 knockout (KO) mice had a higher number of regenerating crypts in the jejunum than did Gpx2-KO or wild-type mice analyzed 4 days after $10 Gy g-irradiation. Without g-irradiation, glutathione peroxidase (GPX) activity in the jejunal and ileal epithelium of Gpx1-KO mice was ,10 and ;35%, respectively, of that of the wildtype mice. Four days after exposure to 11 Gy, GPX activity in wild-type and Gpx1-KO ileum was doubled and tripled, respectively. However, jejunal GPX activity was not changed. Thus the lack of GPX activity in the jejunum is associated with better regeneration of crypt epithelium after radiation. Gpx2 gene expression was solely responsible for the increase in GPX activity in the ileum, since radiation did not alter GPX activity in Gpx2-KO mice. The intestinal Gpx2 mRNA levels of Gpx1-KO and wild-type mice increased up to 14and 7-fold after radiation, respectively. Although the Gpx1-KO jejunum had higher levels of PGE2 than the wild-type jejunum after exposure to 0 or 15 Gy, these differences were not statistically significant. Thus whether GPX inhibits PG biosynthesis in vivo remains to be established. We can conclude that the Gpx2 gene compensates for the lack of Gpx1 gene expression in the ileal epithelium. This may have abolished the protective effect in Gpx1-KO mice against the radiation damage in the ileum.