RESUMO
Involvement of individual JAK kinases in the realization of growth potential of mesenchymal progenitor cells was examined in vitro. Important role of JAK2 and JAK3 in determining the initial level of mitotic activity of progenitor cells was established. The yield of fibroblast CFUF was suppressed under the effect of specific inhibitors of JAK kinases. Blockade of JAK3 increased the rate of progenitor element differentiation. JAK1 had no effect on proliferation and differentiation status of progenitor cells.
Assuntos
Diferenciação Celular , Proliferação de Células , Janus Quinases/fisiologia , Células-Tronco Mesenquimais/enzimologia , Animais , Células Cultivadas , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos Endogâmicos CBARESUMO
We studied the mechanisms of erythropoiesis stimulation and effectiveness of Poetam, a preparation containing release-active anti-erythropoietin antibodies as a supplement treatment for experimental iron deficiency anemia during gestation. The results confirmed potency of combined therapy to stimulate erythropoiesis, which was more efficacious in comparison with monotherapy as assessed by the count of erythrokaryocytes and erythroid progenitors in the hematopoietic tissue as well as by the content of erythrocytes and hemoglobin in the peripheral blood. Activation of erythropoiesis is related to the modulatory effect of Poetam on proliferative activity and differentiation of erythroid precursors, which in most aspects results from stimulatory action of Poetam on secretion of the hematopoietically active factors by adherent elements of the hematopoietic microenvironment.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Anticorpos/farmacologia , Complicações na Gravidez/tratamento farmacológico , Anemia Ferropriva/sangue , Animais , Anticorpos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Contagem de Eritrócitos , Células Eritroides/efeitos dos fármacos , Eritropoese/efeitos dos fármacos , Feminino , Camundongos Endogâmicos C57BL , Gravidez , Complicações na Gravidez/sangueRESUMO
We studied the dynamics of erythropoiesis in CBA mice during gestation against the background of treatment with iron-binding drug. The mechanisms of suppression of the bone marrow erythroid stem were evaluated. Administration of deferoxamine in a dose of 1 g/kg induced hypoplasia of the erythroid hemopoietic lineage. Suppression of bone marrow erythropoiesis manifested in a decrease of hemoglobin concentration and counts of reticulocytes, erythrocytes, and erythrokaryocytes. These changes were accompanied by a decrease in functional activity of erythropoietic precursors and secretion of erythropoietically active humoral factors by bone marrow myelokaryocytes. These data indicate that deferoxamine can be used for modeling of iron defi ciency anemia in pregnancy.
Assuntos
Anemia Ferropriva/induzido quimicamente , Medula Óssea/efeitos dos fármacos , Desferroxamina/farmacologia , Eritropoese/efeitos dos fármacos , Eritropoese/fisiologia , Sideróforos/farmacologia , Animais , Contagem de Células Sanguíneas , Medula Óssea/metabolismo , Eritrócitos/citologia , Feminino , Camundongos , Camundongos Endogâmicos CBA , Gravidez , Reticulócitos/citologiaRESUMO
PI3- and MAP-kinase signaling pathways duplicate and interchange each other in production of agents that determine total erythropoietic activity under conditions of balanced erythropoiesis. The alternative p38-dependent MAP-kinase pathway is the major regulator of erythropoietic activity of adherent bone marrow cells. Blockade of PI3K and p38 signaling pathways stimulated production of erythropoietin by cells that do not produce it constitutively.
Assuntos
Eritropoese/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Animais , Cromonas/farmacologia , Eritropoese/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Flavonoides/farmacologia , Células-Tronco Hematopoéticas/metabolismo , Imidazóis/farmacologia , Separação Imunomagnética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfolinas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
The role of cAMP- and IKK-2-dependent pathways in stimulation of the growth capacity of mesenchymal progenitor cells with alkaloid songorine was studied in vitro. Inhibitors of adenylate cyclase and IKK-2 were shown to abolish the increase in proliferative activity of progenitor cells. Moreover, blockade of the inhibitory kinase complex was accompanied by a decrease in the intensity of progenitor cell differentiation.
Assuntos
Adenilil Ciclases/genética , Alcaloides/farmacologia , AMP Cíclico/metabolismo , Quinase I-kappa B/genética , Células-Tronco Mesenquimais/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , AMP Cíclico/antagonistas & inibidores , Didesoxiadenosina/análogos & derivados , Didesoxiadenosina/farmacologia , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica , Quinase I-kappa B/antagonistas & inibidores , Quinase I-kappa B/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos CBA , Cultura Primária de Células , Transdução de Sinais , Células-Tronco , Tiofenos/farmacologiaRESUMO
The role of JNK-mediated signal pathway and participation of p53 transcription factor in stimulation of mesenchymal precursor cell function by the fibroblast growth factor was studied. The levels of fibroblast colony- and cluster formation and proliferative activity of mesenchymal precursors increased in response to JNK and p53 specific inhibitors. JNK and p53 blockers did not change the rate of fibroblast growth factor-induced progenitor element differentiation.
Assuntos
Fatores de Crescimento de Fibroblastos/fisiologia , MAP Quinase Quinase 4/metabolismo , Células-Tronco Mesenquimais/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Animais , Proliferação de Células , Células Cultivadas , Masculino , Camundongos Endogâmicos CBA , Transdução de SinaisRESUMO
We studied the role of intracellular signaling molecules PI3K, ÐÐÐ K ERK1/2, and Ñ38 in stimulation of realization of the growth potential of mesenchymal progenitor cells by alkaloid songorine in vitro. Inhibitors of PI3K, ERK1/2 and Ñ38 canceled the increase in proliferative activity of progenitor cells, the blockers of ERK1/2 and Ñ38 reduced the intensity of progenitor cell differentiation.
Assuntos
Alcaloides/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/enzimologia , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Cromonas/farmacologia , Ensaio de Unidades Formadoras de Colônias , Flavonoides/farmacologia , Imidazóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/enzimologia , Camundongos , Camundongos Endogâmicos CBA , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/fisiologia , Modelos Biológicos , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/fisiologia , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologiaRESUMO
Specific JNK and p53 inhibitors stimulated the formation of fibroblast colonies (CFU-F) and clusters (ClFU-F) and increased proliferative activity of mesenchymal progenitor cells. No effects of inhibitors of JNK and p53 on differentiation of progenitor elements were revealed.
Assuntos
Benzotiazóis/farmacologia , Proliferação de Células/fisiologia , MAP Quinase Quinase 4/antagonistas & inibidores , Células-Tronco Mesenquimais/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/fisiologia , Tolueno/análogos & derivados , Proteína Supressora de Tumor p53/antagonistas & inibidores , Animais , Proliferação de Células/efeitos dos fármacos , Hidroxiureia , Técnicas In Vitro , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos CBA , Estatísticas não Paramétricas , Tolueno/farmacologiaRESUMO
The involvement of PI3K, ERK and p38-dependent signaling system in the regulation of functional activity of erythroid precursors after blood loss (30% of circulating volume) was studied. We demonstrated the important role of PI3K and p38 in the suppression of differentiation of erythroid precursors the contribution of p38 to stimulation of mitotic activity of erythroid CFU, which maintains the growth potential of the precursors at the optimal physiological level. The classical MAPK/ERK-kinase pathway does not determine the proliferative and differentiation status of erythroid CFU.
Assuntos
Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Precursoras Eritroides/fisiologia , Hemorragia/fisiopatologia , Sistema de Sinalização das MAP Quinases/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Ensaio de Unidades Formadoras de Colônias , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estatísticas não ParamétricasRESUMO
We studied the role of signaling pathways in the regulation of erythropoiesis against the background of myelosuppression caused by administration of 5-fluorouracil. The important role of cyclic AMP in the maturation of erythroid progenitors after cytostatic treatment was demonstrated. The secretory activity of myelokaryocytes during the period of erythroid hemopoiesis recovery is mainly regulated via the p38 MAPK signaling pathway; non-erythropoietin factors are involved in the formation of erythropoietic activity of adherent cells of the microenvironment.