RESUMEN
The features of the participation of Smad3 in the functioning of neural stem cells (NSC), neuronal committed precursors (NCP), and neuroglial elements were studied in vitro. It was found that this intracellular signaling molecule enhances the clonogenic and proliferative activities of NCP and inhibits specialization of neuronal precursors. At the same time, Smad3 does not participate in the realization of the growth potential of NSC. With regard to the secretory function (production of neurotrophic growth factors) of neuroglial cells, the stimulating role of Smad3-mediated signaling was shown. These results indicate the promise of studying the possibility of using Smad3 as a fundamentally new target for neuroregenerative agents.
Asunto(s)
Proliferación Celular , Células-Madre Neurales , Neuroglía , Proteína smad3 , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Proteína smad3/metabolismo , Proteína smad3/genética , Animales , Neuroglía/metabolismo , Neuroglía/citología , Proliferación Celular/fisiología , Transducción de Señal , Diferenciación Celular/fisiología , Células Cultivadas , Ratas , Neuronas/metabolismo , Neuronas/citología , RatonesRESUMEN
We analyzed the content and functional activity of various types of regenerative-competent cells of the subventricular zone of the cerebral hemispheres in experimental mice under conditions of in vitro modeling of ß-amyloid-induced neurodegeneration. Fundamentally different (opposite) effects of ß-amyloid on functional activity of multipotent neural stem cells (NSC) and neuronal committed progenitors (NCP) were revealed. ß-Amyloid suppressed proliferation of NSC and stimulated their differentiation. At the same time, an increase in the mitotic activity of NCP was observed with a decrease in the intensity of their specialization. These changes in the functioning of progenitor cells developed against the background of a significant drop in the production of neurotrophic growth factors by neuroglia. These phenomena indicate marked discoordination of the activity of regenerative-competent cells of various types.
Asunto(s)
Péptidos beta-Amiloides , Células-Madre Neurales , Ratones , Animales , Péptidos beta-Amiloides/metabolismo , Neuronas/metabolismo , Neuroglía/metabolismo , Diferenciación Celular , Factores de Crecimiento Nervioso/metabolismoRESUMEN
We studied the role of JAKs and STAT3 in the growth potential of neural stem cells and the humoral neurotrophic function of neuroglia in modeling ß-amyloid-induced neurodegeneration in vitro. It was found that these signaling molecules do not participate in the neural stem cell functioning, and JAKs plays an inhibitory role (realized, however, without STAT3) in the secretion of neurotrophins by glial cells under conditions of their optimal vital activity. The effect of ß-amyloid on progenitor cells is accompanied by the appearance of a "negative" effect of STAT3 signaling pathway on their proliferative activity. At the same time, JAKs and STAT3 during neurodegeneration stimulate specialization/differentiation of neural stem cells and production of growth factors by neuroglial cells. These results indicate the possibility of stimulating proliferation of neural stem cells coupled with their differentiation by using selective STAT3 inhibitors.
Asunto(s)
Tejido Nervioso , Células-Madre Neurales , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/farmacología , Diferenciación Celular , Quinasas Janus/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
The role of ERK1/2 and p38 in the realization of the growth potential of neural stem cells and secretion of neurotrophic growth factors by glial cells was studied using in vitro model of ß-amyloid-induced neurodegeneration. It was shown that amyloid-ß fragment 25-35 significantly inhibits the cell cycle progression of neural stem cells against the background of stimulation of their differentiation and reduced production of growth factors by neuroglia. The inhibitory role of ERK1/2 and p38 in relation to the proliferative activity of neural stem cells and the secretory activity of glial elements was revealed. ERK1/2 and p38 inhibitors increased proliferation of progenitor cells of the nervous tissue and reduced the intensity of their specialization, as well as stimulated production of growth factors by neuroglial cells under conditions of simulated ß-amyloid-induced neurodegeneration.
Asunto(s)
Sistema de Señalización de MAP Quinasas , Células-Madre Neurales , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/farmacología , Diferenciación Celular , Células-Madre Neurales/metabolismo , Neuroglía/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
The results of studying the effect of the anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice with Lewis lung carcinoma against the background of doxorubicin administration were presented. It was shown that administration of the anthocyanin-containing complex from S. aucuparia L. to animals with the tumor prevented the development of anemic syndrome by promoting regeneration of the erythropoiesis after its depletion caused by single administration of a cytostatic agent.
Asunto(s)
Carcinoma Pulmonar de Lewis , Citostáticos , Sorbus , Animales , Antocianinas/farmacología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Eritropoyesis , RatonesRESUMEN
Pegylated hyaluronate-endo-ß-N-acetylhexosaminidase was shown to potentiate significantly the hemostimulatory effect of pegylated erythropoietin. It was found that enhanced production of hemopoietin by adherent and non-adherent cells of the hemopoiesis-inducing microenvironment and elevated serum content of endogenous erythropoietin along with increased susceptibility of erythroid precursors to pegylated erythropoietin underlay this phenomenon.
Asunto(s)
Anemia/tratamiento farmacológico , Eritropoyetina/farmacología , Hematínicos/farmacología , Polietilenglicoles/farmacología , beta-N-Acetilhexosaminidasas/farmacología , Anemia/inducido químicamente , Animales , Células de la Médula Ósea/efectos de los fármacos , Carboplatino , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Sinergismo Farmacológico , Quimioterapia Combinada , Células Eritroides/efectos de los fármacos , Eritropoyetina/administración & dosificación , Hematínicos/administración & dosificación , Ratones , Ratones Endogámicos CBA , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Células Madre/efectos de los fármacos , Células Madre/fisiología , beta-N-Acetilhexosaminidasas/administración & dosificaciónRESUMEN
Pegylated hyaluronate-endo-ß-N-acetylhexosaminidase considerably potentiates the hemostimulating effects of erythropoietin due to intensification of proliferation and differentiation of erythroid precursors against the background of enhanced secretion of hemopoietins by nonadherent hemopoiesis-inducing environment cells and elevation of serum erythropoietin concentration. The use of the enzyme allows 10-fold reduction of the maximum effective erythropoietin dose.