RESUMO
The vertebrate Wnt-1 proto-oncogene is expressed transiently in embryonic brain and functions in the development of the central nervous system and neural crest. The role of Wnt-1 in neural crest development appears to be to increase the number of certain progenitor cells by preventing their premature differentiation. To study the mechanism by which this transient Wnt-1 expression inhibits differentiation we have constructed PC12 pheochromocytoma cells in which Wnt-1 expression levels were controlled by use of a tetracycline-responsive transactivator. Induction of Wnt-1 expression by tetracycline withdrawal was followed by activation of the Wnt-1 signalling pathway as shown by activation of the Lef-1/Tcf transcription factor. Wnt-1 expression by these cells resulted in reversible inhibition of NGF-induced neurite outgrowth, but it did not adversely affect the maintenance of previously formed NGF-induced neurites. Wnt-1 expression also partially blocked the ability of NGF to decrease the rate of cell multiplication. Wnt-1 decreased the NGF-induced expression of the late-response gene SCG10 but not of the immediate early genes, fos, Nur77 and UPAR (urokinase-type plasminogen activator receptor) nor of the late-response genes GAP-43 and collagenase. The Wnt-1 expressing PC12 cells multiplied at a greater rate when they expressed Wnt-1 than they did in the absence of Wnt-1 expression, a result that is consistent with the proposal that Wnt-1 may also act as a mitogen.
Assuntos
Regulação da Expressão Gênica , Fator de Crescimento Neural/antagonistas & inibidores , Neuritos/metabolismo , Proteínas Proto-Oncogênicas/fisiologia , Proteínas de Peixe-Zebra , Transportadores de Cassetes de Ligação de ATP/metabolismo , Sistema X-AG de Transporte de Aminoácidos , Animais , Proteínas de Ligação ao Cálcio , Proteínas de Transporte , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Receptores Frizzled , Proteína GAP-43/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Genes Precoces/genética , Ácido Glutâmico/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Fator 1 de Ligação ao Facilitador Linfoide , Proteínas de Membrana , Camundongos , Proteínas dos Microtúbulos , Fator de Crescimento Neural/farmacologia , Fatores de Crescimento Neural/genética , Neuritos/efeitos dos fármacos , Células PC12 , Proteínas/genética , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Receptores de Superfície Celular/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Transdução de Sinais/efeitos dos fármacos , Estatmina , Tetraciclina/farmacologia , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/genética , Tirosina 3-Mono-Oxigenase/genética , Proteínas Wnt , Proteína Wnt1RESUMO
Circadian clocks can be reset by light stimulation. To investigate the mechanism of this phase shifting, the effects of light pulses on the protein and messenger RNA products of the Drosophila clock gene period (per) were measured. Photic stimuli perturbed the timing of the PER protein and messenger RNA cycles in a manner consistent with the direction and magnitude of the phase shift. In addition, the recently identified clock protein TIM (for timeless) interacted with PER in vivo, and this association was rapidly decreased by light. This disruption of the PER-TIM complex in the cytoplasm was accompanied by a delay in PER phosphorylation and nuclear entry and disruption in the nucleus by an advance in PER phosphorylation and disappearance. These results suggest a mechanism for how a unidirectional environmental signal elicits a bidirectional clock response.
Assuntos
Relógios Biológicos , Ritmo Circadiano , Proteínas de Drosophila , Drosophila melanogaster/fisiologia , Luz , Proteínas Nucleares/metabolismo , Proteínas/metabolismo , Animais , Relógios Biológicos/genética , Encéfalo/metabolismo , Núcleo Celular/metabolismo , Ritmo Circadiano/genética , Citoplasma/metabolismo , Escuridão , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica , Genes de Insetos , Neurônios/metabolismo , Proteínas Nucleares/genética , Proteínas Circadianas Period , Fosforilação , Células Fotorreceptoras de Invertebrados/metabolismo , Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
A 56-yr-old Japanese man with chronic liver disease was admitted for evaluation of increased serum alpha-fetoprotein reaching levels as high as 7190 ng/ml. The presence of hepatocellular carcinoma was ruled out by computed tomography and hepatic angiography. Laparoscopy and liver biopsy sample showed active liver cirrhosis. alpha-Fetoprotein granules were positive in hepatocytes. The rise in serum alpha-fetoprotein level was transitory and returned to less than 100 ng/ml 4 wk later. It was suggested that regeneration after acute exacerbation of cirrhosis might have been closely related to the dramatic increase in alpha-fetoprotein production.