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










Base de datos
Intervalo de año de publicación
1.
Behav Brain Res ; 442: 114286, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36610548

RESUMEN

Diabetes has been regarded as an independent risk factor for Alzheimer's disease (AD). Our previous study found that diabetes activated autophagy, but lysosome function was impaired. Autophagy-lysosome dysfunction may be involved in Aß deposition in diabetic cognitive impairment. In the present study, we used STZ-induced diabetic rats and SH-SY5Y cells to investigate whether diabetes inhibits autophagosome fusion with lysosomes. We found that in the in vivo study, STZ-induced diabetic rats exhibited cognitive dysfunction, and the lysosome function-related factors CTSL, CTSD, and Rab7 were decreased (P < 0.05). In an in vitro study, the mRFP-GFP-LC3 assay showed that the fusion of autophagosomes with lysosomes was partly blocked in SH-SY5Y cells. High glucose treatment downregulated the number of autophagolysosomes, downregulated CTSD, CTSL, and Rab7 expression (P < 0.05), and then influenced the function of ACP2 to partly block the fusion of autophagosomes and lysosomes to inhibit Aß clearance. These findings indicate that high glucose treatment affected lysosome function, interfered with the fusion of autophagosomes with lysosomes, and partly blocked autophagic flux to influence Aß clearance.


Asunto(s)
Diabetes Mellitus Experimental , Neuroblastoma , Ratas , Humanos , Animales , Autofagosomas/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Neuroblastoma/metabolismo , Autofagia , Lisosomas/metabolismo , Glucosa/metabolismo
2.
Behav Brain Res ; 320: 484-493, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-27773683

RESUMEN

ß-Amyloid (Aß) deposition has a central role in the pathogenesis of Alzheimer disease (AD). Previous studies have indicated that as a risk factor for AD, diabetes mellitus (DM) could induce Aß deposition in the brain, but the mechanism is not fully elucidated. Autophagy-lysosome is a cellular pathway involved in protein and organelle degradation. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether autophagy-lysosome is related to Aß1-42 clearance in DM. We found that DM rats had a longer escape latency and less frequent entry into the target zone than that of the control group (p<0.05) in the Morris water maze test. Meanwhile, hippocampal neuron damage and apoptosis (p<0.05) were found in the DM rats. The Aß1-42 expression in the hippocampus significantly increased in the DM group compared with the control group (p<0.05). The markers of autophagy, beclin-1 and LC3 II, were increased (p<0.05), whereas LC3 I was decreased (p<0.05), and the ratio of LC3 II / I was increased as the time advanced (p<0.01). LAMP1 and LAMP2, which are the markers of lysosome function, were decreased in the hippocampus of DM rats (p<0.05). The Aß1-42 deposition was correlated with beclin-1, LC3 II, and LC3 I positively (p<0.05), but with LAMP1 and LAMP2 negatively (p<0.05). These findings indicate that DM activated autophagy, but lysosome function was impaired. Autophagy-lysosome dysfunction may be involved in the Aß deposition in diabetic cognitive impairment.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Antibióticos Antineoplásicos/toxicidad , Autofagia/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Lisosomas/efectos de los fármacos , Fragmentos de Péptidos/metabolismo , Estreptozocina/toxicidad , Animales , Encéfalo/patología , Encéfalo/ultraestructura , Diabetes Mellitus Experimental/patología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Etiquetado Corte-Fin in Situ , Lisosomas/ultraestructura , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , ARN Mensajero , Ratas , Ratas Sprague-Dawley
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...