Comparison of Changes in the Gene Expression of Transferrin Receptor-1 and Other Iron Regulatory Proteins in the Rat Liver and Brain during Acute-Phase-Response.
Ihtzaz Malik, Naila Naz, Nadeem Sheikh, Sajjad Khan, Giuliano Ramadori. University Hospital Goettingen, Germany
Background: Acute phase is clinically characterized by homeostatic alterations such as adinamia, fever, muscular weakness and leucocytosis. Several organs are involved in dramatic changes of iron metabolism such as liver and brain.
Design: Rats were administered turpentine oil (TO) intramuscularly and sacrificed at different time points thereafter. Liver and brain were taken and immediately frozen in liquid nitrogen. Hepatocytes and Kuppfer cells were isolated from normal rat liver. Liver and brain tissue were used for immunohistochemistry, western blot and RNA isolation. RNA from liver and brain tissue was studied by polymerase chain reaction (PCR).
Results: Tissue iron content in the liver and brain increased progressively after the TO administration.By means of immunohistology, an abundant TfR1 expression was detected in membrane and cytoplasm of the liver cells, in contrast to only nuclear expression of TfR1 in the brain and the expression TfR1 increased at protein and RNA level in both organs. In addition, hepcidin-, ferritin H-, divalent-metal transporter-, hephaestin- together with heme oxygenase-1 gene expression was also significantly upregulated while hemojuvelin-, ferroportin-1-, and HFE gene expression was significantly downregulated at the same time points both in the brain and in the liver at RNA level. However, in contrast to what is observed in the liver, expression of main acute phase cytokines (interleukin-6, tumor-necrosis-factor-alpha) in the brain was significantly upregulated.
Conclusions: During acute-phase, iron accumulates in the liver and in the brain and gene expression of TfR1 and iron metabolism proteins is regulated in a way similar to that observed in the liver by locally produced acute-phase cytokines.
Category: Liver & Pancreas
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 184, Wednesday Morning