Characteristics of in vivo murine erythropoietic response to sodium orthovanadate.
Current knowledge about the effects of vanadium compounds on erythropoiesis is still reduced and even contradictory. The aim of this work was to evaluate the in vivo effects of a single dose of sodium orthovanadate (OV, 33 mg/kg i.p.) on CF-1 mice in a time course study (0-8 days). Murine erythropoiesis was assessed through a combinatory of experimental approaches. Classical peripheral and bone marrow (BM) hematological parameters were determined. Erythroid maturation in blood stream and hemopoietic tissues (59Fe uptake assays), BM erythroid progenitor frequency (clonogenic assays) and erythroid crucial protein expressions for commitment and survival: GATA-1, erythropoietin receptor (Epo-R) and Bcl-xL (immunoblottings) were evaluated. Neither BM cellularities nor BM viabilities changed noticeably during the study. Peripheral reticulocytes showed a biphasic increment on days 2 and 8 post-OV. hematocrits enhanced transiently between days 2 and 4. 59Fe uptake percentages enhanced in peripheral blood nearly two-fold over control values between 4 and 8 days (p<0.01) without changes in BM and spleen. Additionally, mature erythroid BM compartments: polychromatophilic erythroblasts and orthochromatic normoblasts increased by the eighth day. BFU-E colonies remained near basal values during the whole experience, whilst CFU-E colonies raised 60% over control at 8 days post-OV (p<0.05). GATA-1 and Epo-R were significantly over-expressed from the third until the end of the experimental protocol (p<0.01). Surprisingly, Bcl-xL showed a constitutive expression pattern without changes during the experience. Experimental data let us suggest that OV does not to cause bone marrow cytotoxicity and that it accelerates maturation of BM committed erythroid precursors. Moreover, there are significant correlations among erythroid-related protein expressions: GATA-1 and Epo-R and the frequency of CFU-E. In addition, Bcl-xL expression invariance during the time course study would indicate that the stimulatory effect of OV treatment on erythropoiesis was mainly exerted on the maturation of red cell precursors rather than on the antiapoptosis of erythroid terminal progenitors.
Aguirre
María Victoria
MV
Department of Biochemistry, Faculty of Medicine, Northeast National University, Moreno 1240, 3400 Corrientes, Argentina.
Juaristi
Julián Antonio
JA
Alvarez
Mirta Alba
MA
Brandan
Nora Cristina
NC
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation; D006403:Hematologic Tests; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000378:metabolism; D012156:Reticulocytes / Q000378:metabolism; D013997:Time Factors; D014638:Vanadates / Q000633:toxicity*
D019253:Proto-Oncogene Proteins c-bcl-2; D017467:Receptors, Erythropoietin; D014638:Vanadates