title: Differential regulation of ferritin subunits and iron transport proteins: an effect of targeted hepatic X-irradiation.
abstract: The current study aimed to investigate radiation-induced regulation of iron proteins including ferritin subunits in rats. Rat livers were selectively irradiated in vivo at 25 Gy. This dose can be used to model radiation effects to the liver without inducing overt radiation-induced liver disease. Sham-irradiated rats served as controls. Isolated hepatocytes were irradiated at 8 Gy. Ferritin light polypeptide (FTL) was detectable in the serum of sham-irradiated rats with an increase after irradiation. Liver irradiation increased hepatic protein expression of both ferritin subunits. A rather early increase (3 h) was observed for hepatic TfR1 and Fpn-1 followed by a decrease at 12 h. The increase in TfR2 persisted over the observed time. Parallel to the elevation of AST levels, a significant increase (24 h) in hepatic iron content was measured. Complete blood count analysis showed a significant decrease in leukocyte number with an early increase in neutrophil granulocytes and a decrease in lymphocytes. In vitro, a significant increase in ferritin subunits at mRNA level was detected after irradiation which was further induced with a combination treatment of irradiation and acute phase cytokine. Irradiation can directly alter the expression of ferritin subunits and this response can be strongly influenced by radiation-induced proinflammatory cytokines. FTL can be used as a serum marker for early phase radiation-induced liver damage.
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center, Georg-August University, Robert-Koch Straße 40, 37075 Göttingen, Germany ; Department of Radiation Therapy and Radiooncology, University Medical Center, Georg-August University, Robert-Koch-Straße 40, 37075 Göttingen, Germany.
authors.forename: Naila
authors.identifier: 0000-0002-8864-0250
authors.initials: N
authors.lastname: Naz
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center, Georg-August University, Robert-Koch Straße 40, 37075 Göttingen, Germany.
authors.forename: Shakil
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center, Georg-August University, Robert-Koch Straße 40, 37075 Göttingen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Cameron
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center, Georg-August University, Robert-Koch Straße 40, 37075 Göttingen, Germany.
authors.forename: Federico
authors.initials: F
authors.lastname: Moriconi
authors.affiliation: Department of Radiation Therapy and Radiooncology, University Medical Center, Georg-August University, Robert-Koch-Straße 40, 37075 Göttingen, Germany.
authors.forename: Margret
authors.identifier: 0000-0002-3369-1237
authors.initials: M
authors.lastname: Rave-Fränk
authors.affiliation: Department of Radiation Therapy and Radiooncology, University Medical Center, Georg-August University, Robert-Koch-Straße 40, 37075 Göttingen, Germany ; Department of Radiation Oncology, Medizinische Hochschule Hannover, Carl-Neuberg Straße, 30625 Hannover, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
authors.affiliation: Department of Radiation Therapy and Radiooncology, University Medical Center, Georg-August University, Robert-Koch-Straße 40, 37075 Göttingen, Germany.
authors.forename: Clemens Friedrich
authors.initials: CF
authors.lastname: Hess
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center, Georg-August University, Robert-Koch Straße 40, 37075 Göttingen, Germany.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center, Georg-August University, Robert-Koch Straße 40, 37075 Göttingen, Germany.
authors.forename: Ihtzaz A
authors.initials: IA
authors.lastname: Malik
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000528:radiation effects*; D027682:Cation Transport Proteins / Q000096:biosynthesis; D005293:Ferritins / Q000097:blood / Q000235:genetics*; D005786:Gene Expression Regulation / Q000528:radiation effects; D022781:Hepatocytes / Q000378:metabolism / Q000528:radiation effects; D007501:Iron / Q000097:blood*; D008099:Liver / Q000378:metabolism* / Q000528:radiation effects; D051381:Rats; D011990:Receptors, Transferrin / Q000096:biosynthesis; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D011990:Receptors, Transferrin; C548977:Tfr2 protein, rat; C545564:Tfrc protein, rat; D000098742:Ferroportin; D005293:Ferritins; D007501:Iron