title: Comparison of changes in gene expression of transferrin receptor-1 and other iron-regulatory proteins in rat liver and brain during acute-phase response.
abstract: The "acute phase" is clinically characterized by homeostatic alterations such as somnolence, adinamia, fever, muscular weakness, and leukocytosis. Dramatic changes in iron metabolism are observed under acute-phase conditions. Rats were administered turpentine oil (TO) intramuscularly to induce a sterile abscess and killed at various time points. Tissue iron content in the liver and brain increased progressively after TO administration. Immunohistology revealed an abundant expression of transferrin receptor-1 (TfR1) in the membrane and cytoplasm of the liver cells, in contrast to almost only nuclear expression of TfR1 in brain tissue. The expression of TfR1 increased at the protein and RNA levels in both organs. Gene expression of hepcidin, ferritin-H, iron-regulatory protein-1, and heme oxygenase-1 was also upregulated, whereas that of hemojuvelin, ferroportin-1, and the hemochromatosis gene was significantly downregulated at the same time points in both the brain and the liver at the RNA level. However, in contrast to observations in the liver, gene expression of the main acute-phase cytokine (interleukin-6) in the brain was significantly upregulated. In vitro experiments revealed TfR1 membranous protein expression in the liver cells, whereas nuclear and cytoplasmic TfR1 protein was detectable in brain cells. During the non-bacterial acute phase, iron content in the liver and brain increased together with the expression of TfR1. The iron metabolism proteins were regulated in a way similar to that observed in the liver, possibly by locally produced acute-phase cytokines. The significance of the presence of TfR1 in the nucleus of the brain cells has to be clarified.
authors: Department of Internal Medicine, Division of Gastroenterology and Endocrinology, University Medical Center Göttingen, Göttingen, Germany. i.malik@med.uni-goettingen.de
authors: Ihtzaz Ahmed
authors: IA
authors: Malik
authors: Naila
authors: N
authors: Naz
authors: Nadeem
authors: N
authors: Sheikh
authors: Sajjad
authors: S
authors: Khan
authors: Federico
authors: F
authors: Moriconi
authors: Martina
authors: M
authors: Blaschke
authors: Giuliano
authors: G
authors: Ramadori
mesh_terms: D000210:Acute-Phase Reaction / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D000071020:Hemochromatosis Protein; D022781:Hepatocytes / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011990:Receptors, Transferrin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
chemical_list: D023181:Antimicrobial Cationic Peptides; D058851:GPI-Linked Proteins; C578702:HAMP protein, human; C578703:Hamp protein, rat; D000071020:Hemochromatosis Protein; D064451:Hepcidins; C513726:Hjv protein, rat; D035925:Iron-Regulatory Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; C545564:Tfrc protein, rat; D007501:Iron