RESUMO
Mutations in lamin A/C gene (LMNA) lead to development of severe disorders--laminopathies. Unlike most other types of intermediate filaments, where the pathological effect of mutations is tightly linked to alteration of mechanical and integrative functions, the detailed mechanism of lamin mutations is still unclear and possibly involves the alteration of nuclear signaling and transcriptional processes. Since the mesenchymal lineage tissues such as myocardium, skeletal muscle, adipose and bone tissues are mostly affected in laminopathies, the role of lamin A/C in differentiation process of mesenchymal stem cells has been assumed. The aim of the study was to estimate the effect of LMNA mutations of differentiation of mesenchymal stem cells into adipose lineages. In vitro mitagenesis was performed on wild type LMNA gene incorporated in a lentiviral vector. Several previously described mutations in LMNA were used, each associated with a certain phenotype. Adipose-derived mesenchymal stem cells from healthy donors were transduced with lentiviruses bearing either wild-type or mutant LMNA. Cells were then induced to adipose differentiation. We show that mutant LMNA/C promotes differentiation capacity of mesenchymal stem cells as seen by morphological changes and by expression of specific adipose markers.
Assuntos
Tecido Adiposo/citologia , Diferenciação Celular/genética , Lamina Tipo A/genética , Células-Tronco Mesenquimais/citologia , Linhagem da Célula , Humanos , Células-Tronco Mesenquimais/metabolismo , MutaçãoRESUMO
The possibility of differentiation of insulin-producing cells and neural and glial elements was demonstrated in the culture of bone marrow stromal cells. The perspectives of use of the bone marrow stromal cells in clinical medicine are considered.
Assuntos
Células da Medula Óssea/fisiologia , Transplante de Células/métodos , Epilepsia/terapia , Células-Tronco Pluripotentes/fisiologia , Células Estromais/fisiologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Diabetes Mellitus/terapia , Humanos , Insulina/metabolismo , Células de Langerhans/citologia , Células de Langerhans/efeitos dos fármacos , Células de Langerhans/metabolismo , Camundongos , Neurônios/citologia , Pâncreas/citologia , Células-Tronco Pluripotentes/citologia , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Tretinoína/farmacologiaRESUMO
The in vitro induced differentiation of mouse bone marrow stromal cells into nerve cells by retinoic acid and leukemia inhibitory factor has been shown, using morphological, histochemical and immunocytochemical analyses. The developed techniques allow to obtain up to 30% of neural cells in vitro. A suggestion about pluripotency of bone marrow stromal cells and possibility of their application to the cell therapy is discussed.
Assuntos
Células da Medula Óssea/citologia , Neurônios/citologia , Células Estromais/citologia , Animais , CamundongosRESUMO
The results of investigation of haptoglobin (Hp) types in 596 donor blood samples in some towns of Ukraine (Dnepropetrovsk, Kharkov, Odessa, Kiev, Uzhgorod, Zhitomir) are presented. Three normal Hp types (Hp1-1, Hp2-1 and Hp2-2) have been found. The reliable interpopulation differences in the Hp types frequency were not found. On the whole the Hp types frequency in the type Hp1-1 comprised 12.7%. In the type Hp2-1-48.1% and in the type Hp2-2-36.5%. The frequency of the gene Hp1 is 0.38. The frequency of the Hp types and of the gene Hpl in Ukraine is similar to that in population of Eastern Europe and European Part of Russia.
Assuntos
Genética Populacional , Haptoglobinas/genética , Doadores de Sangue/estatística & dados numéricos , Eletroforese das Proteínas Sanguíneas/estatística & dados numéricos , Humanos , Fenótipo , Ucrânia , População Urbana/estatística & dados numéricosAssuntos
Hormônios/fisiologia , Próstata/crescimento & desenvolvimento , Receptores Androgênicos , Animais , Di-Hidrotestosterona/farmacologia , Di-Hidrotestosterona/fisiologia , Relação Dose-Resposta a Droga , Estrogênios/farmacologia , Estrogênios/fisiologia , Hormônios/farmacologia , Humanos , Masculino , Hormônios Hipofisários/farmacologia , Hormônios Hipofisários/fisiologia , Próstata/efeitos dos fármacos , Receptores de Esteroides/efeitos dos fármacos , Receptores de Esteroides/fisiologia , Testosterona/farmacologia , Testosterona/fisiologiaRESUMO
Experiments in vito showed that indicators of prostatic growth (organ mass, protein content, DNA) and function (acid phosphatase activity) of castrated rats regenerated under the influence of 5 alpha-dihydrotestosterone. The morphological structure of this organ showed a pronounced activation of the glandular epithelium proliferation by this metabolite without a significant effect on the connective tissue. The other testosterone metabolite 5 alpha-androstan-3 beta, 17 beta-diol did not influence biochemical indicators but according to the morphological data it stimulated the secretory activity of the glandular epithelium and connective tissue formation. As a result of a combined effect of the metabolites the influence of 5 alpha-dihydrotestosterone on the proliferative processes in the prostate was limited, and the response of the connective tissue to 5 alpha-androstan-3 beta, 17 beta-diol preserved. The results obtained were not in accord with a hypothesis that 5 alpha-dihydrotestosterone is the only physiologically active testosterone metabolite in the rat pancreas, and confirmed the idea of androgen functional interrelationship.
Assuntos
Androstano-3,17-diol/administração & dosagem , Androstanóis/administração & dosagem , Di-Hidrotestosterona/administração & dosagem , Orquiectomia , Próstata/metabolismo , Fosfatase Ácida/metabolismo , Animais , DNA/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/crescimento & desenvolvimento , Proteínas/metabolismo , Ratos , Ratos EndogâmicosRESUMO
The acid phosphatase is studied in the prostate gland of rats. It is shown that 10 days after gonadectomy the activity of acid phosphatase lowered considerably. Administration of testosterone propionate or 5 alpha-dihydrotestosterone to castrated animals restored the enzyme activity whereas 5 alpha-androstan-3 beta,17-diol was not effective. Administration of testosterone propionate with one of its metabolites increased the activity of acid phosphatase in the prostate gland, however to a less extent than with the use of the hormone itself. The lowest activity is detected with the simultaneous application of three androgens.
Assuntos
Fosfatase Ácida/metabolismo , Androstano-3,17-diol/farmacologia , Androstanóis/farmacologia , Castração , Di-Hidrotestosterona/farmacologia , Próstata/enzimologia , Testosterona/farmacologia , Animais , Sinergismo Farmacológico , Ativação Enzimática/efeitos dos fármacos , Masculino , Ratos , Ratos EndogâmicosRESUMO
The results are presented of studying nucleic acid and protein synthesis in the rabbit prostate. It was shown that incorporation of radioactive precursors into the prostate DNA, RNA and proteins is diminished two months after gonadectomy of the animals. Testosterone and its metabolite 5 alpha-dihydrotestosterone markedly intensify RNA and protein synthesis in the prostate of castrated rabbits, whereas 5 alpha-dihydrotestosterone only exerts a stimulating effect upon DNA synthesis. Preliminary testosterone propionate injections to gonadectomized rabbits delay DNA synthesis, induced by 5 alpha-dihydrotestosterone, and decrease the marker incorporation into RNA and protein, comparatively to the effect of each separate androgen.