Low glutathione peroxidase activity in Gpx1 knockout mice protects jejunum crypts from gamma-irradiation damage.
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 > or =10 Gy gamma-irradiation. Without gamma-irradiation, glutathione peroxidase (GPX) activity in the jejunal and ileal epithelium of Gpx1-KO mice was <10 and approximately 35%, respectively, of that of the wild-type 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 14- and 7-fold after radiation, respectively. Although the Gpx1-KO jejunum had higher levels of PGE(2) 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.
Department of Medical Oncology, City of Hope Medical Center, Duarte, CA 91010, USA.
R S
RS
Esworthy
J R
JR
Mann
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Sam
F F
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Chu
D000818:Animals; D015152:Blotting, Northern; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D005720:Gamma Rays; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism*; D007082:Ileum / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D007413:Intestinal Mucosa / Q000502:physiology / Q000528:radiation effects; D007583:Jejunum / Q000166:cytology / Q000502:physiology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D011878:Radiotherapy / Q000009:adverse effects; D012038:Regeneration / Q000502:physiology; D000094765:Glutathione Peroxidase GPX1
D012333:RNA, Messenger; C492172:Gpx2 protein, mouse; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse