cGMP-abhängige Proteinkinase und Eisenmetabolismus
Zusammenfassung der Projektergebnisse
The goal of this project was to elucidate the mechanism(s) that induces anemia in cGKI-/- mice. Following subgoals were investigated: a) Does the PPI treatment of cGKI-/- mice that prolongs survival effects the spleen iron content of the cGKI-/- mice or not? b) How does the reduced iron content in the spleen correlate to the iron content in other organs that are involved in iron metabolism i.e. liver and macrophages? c) Is it possible to increase the iron content of the cGKI -/- mice by prolonged i.m. iron injection? d) Is potentially reduced iron absorption caused by an inadequate secretion of hepcidin? e) Are the cytokine levels altered in cGKI-/- mice? Would this cause an inadequate production of hepcidin? f) The lack of the cGKI kinase affects the function of which cell type that may explain the iron phenotype? Is this cell a macrophage? We have investigated these questions and reported that erythrocytes from wild type animals did not express the cGKI protein making an erythrocyte specific cause for the anemia less likely. Both types of animals had bleeding duodenal ulcers. The KO animals had a reduced number of erythrocytes, reduced hemoglobin concentration, an increased number of reticulocytes, and reduced plasma iron concentration. Spleen ferritin light chain protein was extremely reduced. The mRNA for hepatic hepcidin was decreased, where-as the mRNA for transferrin receptor 1 and the iron transporter DMT1 was increased. Injection of iron increased the iron content of spleen and liver as detected by Prussian blue staining and the concentration of ferritin light chain. Intestinal blood loss was prevented by feeding the mice the PPI esomeprazole. Treatment of the mice with PPI normalized all relevant parameters of the anemia. We concluded, cGKI-/- and cGKI RM mice suffer from iron deficiency anemia. Premature degradation of erythrocytes does not cause the anemia.
Projektbezogene Publikationen (Auswahl)
- (2016) Iron deficiency anemia in cGKI-KO mice. Haematologica 101(2):e48-51
Angermeier E, Domes K, Lukowski R, Schlossmann J, Rathkolb B, Hrabě de Angelis M, Hofmann F
(Siehe online unter https://dx.doi.org/10.3324/haematol.2015.137026)
