Increased expression of extracellular glutathione peroxidase in mice with dextran sodium sulfate-induced experimental colitis.
Extracellular glutathione peroxidase (E-GPx) is a selenoenzyme that reduces hydrogen peroxide and organic peroxides. All plasma glutathione peroxidase (GPx) activity in humans is attributable to E-GPx. The gastrointestinal (GI) tract also synthesizes and secretes E-GPx into the extracellular milieu. Endogenously generated oxidants have been implicated in inflammatory bowel disease (IBD). We evaluated E-GPx levels in a mouse model of IBD using dextran sodium sulfate (DSS). Histologic lesions of the lower GI tract consisted of multifocal areas of mucosal erosion denuded of epithelial cells, reduction in goblet cells, dilated crypts, crypt collapse, submucosal edema, and transmural distribution of mixed inflammatory infiltrates. On d 7, plasma GPx activity in the DSS group increased by 61% compared with the control group (p < 0.05). Western blot analysis demonstrated a 64% increase in E-GPx protein in the plasma of the DSS group after 7 d of treatment (p < 0.01). As the major source of plasma GPx is the kidney, we determined whether the increase in plasma GPx activity and protein was caused by a change in E-GPx synthesis by the kidney. After 3 and 7 d of DSS treatment, E-GPx mRNA levels, relative to glyceraldehyde-3-phosphate dehydrogenase, increased in the kidney (p < 0.05) without a concomitant increase in cellular GPx mRNA on d 7. These results suggest that the inflammatory injury in the intestine elicits an increase in E-GPx in the plasma that is associated with an increase in E-GPx mRNA in the kidney. This implies that renal production of E-GPx may be sensitive to insults distal to the kidney.
Tham
Doris M
DM
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA.
Whitin
John C
JC
Cohen
Harvey J
HJ
D000818:Animals; D002432:Cecum / Q000201:enzymology; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology*; D003106:Colon / Q000201:enzymology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004790:Enzyme Induction; D005979:Glutathione Peroxidase / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D015212:Inflammatory Bowel Diseases; D007668:Kidney / Q000201:enzymology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009928:Organ Specificity; D018384:Oxidative Stress; D012333:RNA, Messenger
D012333:RNA, Messenger; D016264:Dextran Sulfate; C116888:Gpx3 protein, mouse; D005979:Glutathione Peroxidase