Nucleoside deaminase: an enzymatic marker for stress erythropoiesis in the mouse

Abstract

A B S T R A C T The level of nucleoside deaminase was determined in extracts of mouse tissues obtained during a period of accelerated erythropoiesis induced by hypoxia, hemorrhage, or the injection of phenylhydrazine. Under these conditions a striking (10-to 100-fold) elevation of the enzyme activity occurred in the spleen. Similar results were obtained with the injection of purified erythropoietin. In control animals, only a trace of nucleoside deaminase activity was detected in the blood. During the reticulocyte response which followed erythropoietic stimulation, there was a sharp increase in the blood level of nucleoside deaminase, which rose up to 120 times that of control animals. By differential centrifugation, the enzyme was localized to the reticulocyte-rich fraction. Erythrocyte nucleoside deaminase remained elevated even after the reticulocyte count had fallen to normal in the phenylhydrazine-treated mice or to zero after the cessation of hypoxia. There was a very gradual decline in the enzyme activity in the blood which fell to the barely detectable control levels about 45 days after the initial reticulocyte response, a time period which corresponds to the survival of the mouse red blood cell. The persistence of high levels of nucleoside deaminase for the full life span of a generation of erythrocytes formed during stress, viewed in contrast to the virtual absence of the enzyme from normal erythrocytes of all ages, represents an enzymatic difference between the normal red blood cell and the cell produced under conditions of accelerated erythropoiesis.

Purine metabolism in murine virus-induced erythroleukemic cells during differentiation in vitro.

“…aminase increased during Me2SO-stimulated differentiation while the activity of the purine biosynthetic enzymes decreased. This elevation in cytidine deaminase activity also occurs during accelerated erythropoiesis in mice and is thought to accompany the development of erythroid cells in vivo (14). The present observation that the specific activity of the PRibN-synthesizing enzymes was repressed in differentiating cells in vitro stresses the importance of these enzymes in the regulation of de novo purine biosynthesis.…”

“…Our earlier studies had shown that, unlike mature erythrocytes, the immature cells in spleens of virus-infected leukemic mice have the enzyme systems required for de novo synthesis of purines and that the activity of the purine biosynthetic enzymes increased in a characteristic pattern during the course of the disease. Similarly, the activity of cytidine deaminase, an enzyme important in pyrimidine metabolism, was comparable in erythroleukemic cells in culture and in the cells of leukemic spleens (9,14).…”

“…Phosphoribosylpyrophosphate amidotransferase [ = amidophosphoribosyltransferase; 5- Changes in cytidine deaminase (cytidine aminohydrolase, EC 3.5.4.5) activity, an enzyme important in the catabolism and reutilization of pyrimidines, were also monitored in this study. Elevation of cytidine deaminase activity has been reported to be associated not only with this virus-induced erythroleukemia, but specifically with accelerated erythroid differentiation in mice during stress erythropoiesis (14).…”

The Assessment of Human Erythroid Output in NOD/SCID Mice Reconstituted with Human Hematopoietic Stem Cells

“…There were no human red cells circulating long term after transplantation, after human red cell infusion, or after splenectomy. The lack of human red cell output may result from one or more of several possibilities: differences in the erythroid stress response (24), low globin gene and protein expression (15,28), lack of human-specific cytokines (19), species differences between human and murine transferrin, or other anti-human inhibitory signals.…”

A sustained and pancellular reversal of gamma-globin gene silencing in adult human erythroid precursor cells

“…5 Alternatively, it was suggested that increased HbF results primarily from accelerated differentiation of developmentally immature erythroblasts that were thought to normally express high levels of gamma-globin. 6 Mechanistic studies of growth-or signaling-related modulation of human fetal hemoglobin are currently not possible in murine models due to well-described differences in the erythroid stress response 7 as well as the inability to detect globin gene or protein expression in the circulating blood of nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice that received transplants of human bone marrow. 8 For these reasons, cultures of primary human erythroblasts are the method of choice for defining relationships between erythroid growth, differentiation, and HbF.…”