metallothionein and Anemia--Hemolytic

Zinc metabolism and metallothionein induction in rat bone marrow were investigated during induced erythropoiesis. Redistribution of body zinc was measured with 65Zn after acute blood loss in rats fed zinc-restricted or zinc-adequate diets. Uptake of 65Zn by bone marrow was related to time after blood loss, metallothionein induction, and dietary zinc status. Increased 65Zn uptake by marrow of zinc-restricted rats suggests a minimal amount of zinc is necessary to support expansion of the erythrocytic compartment. Zinc induction of marrow metallothionein also occurred in rats in which anemia was produced using phenylhydrazine. Anemic rats which were administered zinc had higher concentrations of marrow metallothionein compared with control rats. Induction of marrow metallothionein by zinc in nonanemic rats required prior treatment with erythropoietin. Percoll fractionation showed marrow metallothionein was most abundant in erythroblasts. These experiments suggest metallothionein synthesis occurs in erythropoietin-sensitive precursor cells in the marrow in response to increased zinc accessibility.

Topics: Anemia, Hemolytic; Animals; Biological Transport; Bone Marrow; Erythropoiesis; Erythropoietin; Hematocrit; Hematopoietic Stem Cells; Humans; Liver; Male; Metallothionein; Phenylhydrazines; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Spleen; Zinc

The origin of metallothionein (MT) in red blood cells (RBCs) from a mouse given cadmium was studied in connection with RBC kinetics. Plasma Cd concentration rapidly decreased 3 hr following 109CdCl2 (2 mg/kg, sc) administration, whereas RBC Cd increased from 2 to 4 days, followed by a gradual decrease. RBC Cd was found to be distributed more in the high-molecular-weight fraction than in the MT fraction 12 hr after administration. But, thereafter, Cd increased rapidly in the MT fraction to show changes with time similar to Cd level in RBCs. Hepatic damage induced in a mouse given 21 injections of Cd, with resultant marked elevation of plasma MT concentrations, did not cause any change in RBC Cd concentration. MT was hardly transferred to RBC when a mouse RBC suspension was incubated with mouse hepatic MT. To examine the relationship of Cd-MT and erythropoietic function, mice in the normal group, the phenylhydrazine-induced anemia group (PH), the transfusion-induced plethora group (TR), and the erythropoietin administered plethora group (TR + EP) were given 109CdCl2. Three days after administration, Cd concentration in its RBCs and its MT fraction remarkably increased in the PH group, and was greatly decreased in the TR group. A significant increase was noted in the TR + EP group as compared with the TR group. These results indicate that MT in the RBCs is formed in erythroblasts.

Topics: Anemia, Hemolytic; Animals; Blood Transfusion; Cadmium; Cadmium Chloride; Chromatography, Gel; Erythrocytes; Erythropoiesis; Erythropoietin; Humans; Male; Metallothionein; Mice; Mice, Inbred Strains; Radioisotopes