Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
PLoS One ; 10(9): e0137311, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26340347

RESUMO

The NG2 proteoglycan is characteristically expressed by oligodendrocyte progenitor cells (OPC) and also by aggressive brain tumours highly resistant to chemo- and radiation therapy. Oligodendrocyte-lineage cells are particularly sensitive to stress resulting in cell death in white matter after hypoxic or ischemic insults of premature infants and destruction of OPC in some types of Multiple Sclerosis lesions. Here we show that the NG2 proteoglycan binds OMI/HtrA2, a mitochondrial serine protease which is released from damaged mitochondria into the cytosol in response to stress. In the cytosol, OMI/HtrA2 initiates apoptosis by proteolytic degradation of anti-apoptotic factors. OPC in which NG2 has been downregulated by siRNA, or OPC from the NG2-knockout mouse show an increased sensitivity to oxidative stress evidenced by increased cell death. The proapoptotic protease activity of OMI/HtrA2 in the cytosol can be reduced by the interaction with NG2. Human glioma expressing high levels of NG2 are less sensitive to oxidative stress than those with lower NG2 expression and reducing NG2 expression by siRNA increases cell death in response to oxidative stress. Binding of NG2 to OMI/HtrA2 may thus help protect cells against oxidative stress-induced cell death. This interaction is likely to contribute to the high chemo- and radioresistance of glioma.


Assuntos
Antígenos/metabolismo , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Proteínas Mitocondriais/metabolismo , Proteoglicanas/metabolismo , Serina Endopeptidases/metabolismo , Animais , Anticorpos Neutralizantes/farmacologia , Antígenos/genética , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Cerebelo/patologia , Citosol/efeitos dos fármacos , Citosol/metabolismo , Glioblastoma/genética , Glioblastoma/patologia , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Peróxido de Hidrogênio/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Estresse Oxidativo , Cultura Primária de Células , Ligação Proteica , Proteoglicanas/antagonistas & inibidores , Proteoglicanas/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Serina Endopeptidases/genética , Transdução de Sinais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...