title: Hypoxia-inducible factor-2α and iron absorptive gene expression in Belgrade rat intestine.
abstract: The divalent metal transporter (DMT1, Slc11a2) is an important molecule for intestinal iron absorption. In the Belgrade (b/b) rat, the DMT1 G185R mutation markedly decreases intestinal iron absorption. We used b/b rats as a model to examine the genes that could be compensatory for decreased iron absorption. When tissue hypoxia was assayed by detecting pimonidazole HCl adducts, the b/b liver and intestine exhibited more adducts than the +/+ rats, suggesting that hypoxia might signal altered gene expression. Total RNA in the crypt-villus bottom (C-pole) and villus top (V-pole) of +/+, b/b, and iron-fed b/b rats was isolated for gene array analyses. In addition, hepatic hepcidin and intestinal hypoxia-inducible factor-α (Hifα) expression were examined. The results showed that expression of hepatic hepcidin was significantly decreased and intestinal Hif2α was significantly increased in b/b and iron-fed b/b than +/+ rats. In b/b rats, the expression of Tfrc mRNA in the C-pole and of DMT1, Dcytb, FPN1, Heph, Hmox1, and ZIP14 mRNAs in the V-pole were markedly enhanced with increases occurring even in the C-pole. After iron feeding, the increased expression found in b/b rats persisted, except for Heph and ZIP14, which returned to normal levels. Thus in b/b rats depressed liver hepcidin production and activated intestinal Hif2α starting at the C-pole resulted in increasing expression of iron transport genes, including DMT1 G185R, in an attempt to compensate for the anemia in Belgrade rats.
authors: The Feist-Weiller Cancer Center, Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, 71130, USA.
authors: Kwo-yih
authors: KY
authors: Yeh
authors: Mary
authors: M
authors: Yeh
authors: Paula
authors: P
authors: Polk
authors: Jonathan
authors: J
authors: Glass
mesh_terms: D000740:Anemia / Q000235:genetics / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics*; D015687:Cell Hypoxia; D015870:Gene Expression; D064451:Hepcidins; D007408:Intestinal Absorption / Q000235:genetics* / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D019266:Iron, Dietary / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D000099162:Endothelial PAS Domain-Containing Protein 1; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D023181:Antimicrobial Cationic Peptides; D051792:Basic Helix-Loop-Helix Proteins; D027682:Cation Transport Proteins; D064451:Hepcidins; D019266:Iron, Dietary; D000099162:Endothelial PAS Domain-Containing Protein 1; D000099236:Solute Carrier Family 11, Member 2; C578703:Hamp protein, rat