Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
J Biol Chem ; 291(36): 18663-74, 2016 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-27325701

RESUMO

Xenobiotics exposure increases endoplasmic reticulum (ER) proliferation and cytochrome P-450 (CYP) induction to sustain metabolic requirements. Whether autophagy is essential for the removal of excess ER and CYP and whether an autophagy receptor is involved in this process in mammals remains elusive. In this study, we show that autophagy is induced in mouse livers after withdrawal of the hepatic mitogen 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP). Although isolated autophagosomes, autolysosomes, and lysosomes from mouse livers after withdrawal of TCPOBOP contained ER proteins, those in control mouse livers did not. Liver-specific Atg5 knockout mice had higher basal hepatic ER content that was further increased and sustained after withdrawal of TCPOBOP compared with wild-type mice. In addition to regulating ER degradation, our results also suggest that autophagy plays a role in regulating the homeostasis of hepatic CYP because blocking autophagy led to increased CYP2B10 accumulation either at the basal level or following TCPOBOP withdrawal. Furthermore, we found that the autophagy receptor protein sequestosome 1 (SQSTM1)/p62 is associated with the ER. After withdrawal of TCPOBOP, p62 knockout mice had increased ER content in the liver compared with wild-type mice. These results suggest that p62 may act as an autophagy receptor for the autophagic removal of excess ER in the mouse liver. Taken together, our results indicate that autophagy is important for the removal of excess ER and hepatic CYP enzymes in mouse livers, a process associated with the autophagy receptor protein p62.


Assuntos
Autofagia , Retículo Endoplasmático/metabolismo , Fígado/metabolismo , Proteína Sequestossoma-1/metabolismo , Animais , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Família 2 do Citocromo P450/genética , Família 2 do Citocromo P450/metabolismo , Retículo Endoplasmático/genética , Camundongos , Camundongos Knockout , Piridinas/farmacologia , Proteína Sequestossoma-1/genética , Esteroide Hidroxilases/genética , Esteroide Hidroxilases/metabolismo
2.
Neuroreport ; 13(4): 535-9, 2002 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-11930176

RESUMO

The autosomal recessive mutation wobbler of the mouse (phenotype WR; genotype wr/wr) causes muscular atrophy due to motoneuron degeneration with 100% penetrance on the standard Mus musculus laboratorius C57BL/6J background. In inter- and backcrosses with M. m. castaneus strain CAST/EI we have observed a variability in the severity of neurological symptoms. Approximately 15% of the WR (wr/wr) CAST/B6 hybrids were modified wobbler (WR*) mice defined by an aggravated neuromuscular phenotype with hindlimbs severely affected in addition to forelimbs. Histologically the overt WR* phenotype was paralleled by a caudally extended neurodegeneration in the ventral horn of the spinal cord with severe astrogliosis, and levels of acetylcholine receptor alpha-subunit mRNA in leg muscle much higher than in standard WR mice. Segregation analysis, using 68 polymorphic autosomal markers in a whole genome scan, revealed a major modifier gene locus, termed wrmod1, on chromosome 14. Individual recombination events in chromosome 14 consomic mice narrowed the wrmod1 candidate region to a 29 cM interval between D14MIT154 and D14MIT105, a region homologous to human chromosome 13q. Our analysis provides access to genes that modify neurodegeneration, the human counterparts of which may be responsible for the variable expression of hereditary spinal muscular atrophies.


Assuntos
Camundongos Mutantes Neurológicos/genética , Alelos , Animais , Encéfalo/metabolismo , Mapeamento Cromossômico/métodos , Genótipo , Gliose/genética , Gliose/patologia , Haplótipos/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mutação/genética , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Fenótipo , Medula Espinal/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...