Gene expression in the human small intestine in vivo. Effects of iron-induced lipid peroxidation

Abstract

Imroduction Iron induces lipid peroxidation and the subsequent release of antioxidants in the lumen of the small intestine. This may mediate geue expression in the intestinal waft. The present study aimed to determine which genes are mediated by an iron-induced oxidative challenge in the human small intestine Methods Ten volunteers (22 +/-2 y) were tested on two occasions. Atter an overnight fast, duodenal biopsies, taken in the horizontal part of the duodenum (15 cm distally from the pylorus), were Obtained by duodenoseopy Subsequently, a catheter was inserted into the proximal small intestine ~,ath an injection port positioned in the proximal descending duodenum. After positioning, saline was injected at 10 ml/min and, after reaching steady state, either 80 or 400 mg iron as terrous gluconate was injected for 30 min. Finally, saline was injected for another 60 rain. A second duodenoscopy was pertbrnled to obtain tissue samples after the iron challenges. In the tissue samples, gene expression was measured using Affimetrix U 133A microarray chips (> 20.000 known genes). Resuhs A total number of 9880 genes were expressed in the small intestine. The expression of 91 genes was significantly changed by both the low and the high iron perfusion, whereas 293 genes tended to be regulated by the two iron challenges. Twenty-eight genes were statistically upregulated, whereas 63 genes were significantly dmvnregulated by both iron intervention_s Two of the upregnlated genes serve functions in cell growth and tumor suppression, one gene encodes for sdenoprotein P, which has antioxidant properties, haterestingly, two genes downregnlated by iron are also associated with tumor suppression and negative control of cell proliferation. Conclusion A large number of genes is expressed in the human proximal small intestine. Iron administration, resulting in lipid peroxidation, mediates expression of at least 91 genes in the small bowel.