Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington's disease
Liu Y, Hettinger CL, Zhang D, Rezvani K, Wang X, Wang H
Journal of neurochemistry · 90 citas
Etiquetas de revisión
Solo mecanismosDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Solo mecanismos
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Institutes of Health
- Gobierno
- National Heart, Lung, and Blood Institute
- Gobierno
- National Institute of Neurological Disorders and Stroke
- Gobierno
- NHLBI NIH HHS
- Gobierno
- NINDS NIH HHS
- Gobierno
- NIH
- Subvenciones
- National Heart, Lung, and Blood Institute (R01 HL085629); National Institute of Neurological Disorders and Stroke (R15 NS071459); National Heart, Lung, and Blood Institute (R01HL072166)
Según 6 financiadores declarados.
Publicación
- Publicado
- 2014-01-03 · J Neurochem · vol. 129 · número 3 · págs. 539–547
- Editorial
- Wiley
- Citado
- 133 citas · más que el 95% de estudios similares · 4.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 41 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Endoplasmic Reticulum Stress and Disease · Ubiquitin and proteasome pathways · Autophagy in Disease and Therapy
- Palabras clave
- Sulforaphane, Huntingtin, Proteasome, Huntingtin Protein, Autophagy, Protein degradation, Huntington's disease, Chemistry, Cell biology, Ubiquitin, Proteasome inhibitor, Biology, Molecular biology, Pharmacology, Biochemistry, Mutant, Apoptosis, Medicine, Internal medicine, Disease
- MeSH
- hela cells, animals, mice, transgenic, humans, mice, huntington disease, disease models, animal, isothiocyanates, sulfoxides, proteasome endopeptidase complex, nerve tissue proteins, blotting, western, transfection, autophagy, male, hek293 cells, huntingtin protein
6 autores
- Yanying Liu🇺🇸University of South Dakota
- Casey L. Hettinger🇺🇸University of South Dakota
- Dong Zhang🇺🇸University of South Dakota
- Khosrow Rezvani🇺🇸University of South Dakota
- Xuejun Wang🇺🇸University of South Dakota
- Hongmin Wang🇺🇸University of South Dakota
Resumen
El texto original del estudio, en el idioma en que se publicó.
The ubiquitin proteasome system (UPS) is impaired in Huntington's disease, a devastating neurodegenerative disorder. Sulforaphane, a naturally occurring compound, has been shown to stimulate UPS activity in cell cultures. To test whether sulforaphane enhances UPS function in vivo, we treated UPS function reporter mice ubiquitously expressing the green fluorescence protein (GFP) fused to a constitutive degradation signal that promotes its rapid degradation in the conditions of a healthy UPS. The modified GFP is termed GFP UPS reporter (GFPu). We found that both GFPu and ubiquitinated protein levels were significantly reduced and the three peptidase activities of the proteasome were increased in the brain and peripheral tissues of the mice. Interestingly, sulforaphane treatment also enhanced autophagy activity in the brain and the liver. To further examine whether sulforaphane promotes mutant huntingtin (mHtt) degradation, we treated Huntington's disease cells with sulforaphane and found that sulforaphane not only enhanced mHtt degradation but also reduced mHtt cytotoxicity. Sulforaphane-mediated mHtt degradation was mainly through the UPS pathway as the presence of a proteasome inhibitor abolished this effect. Taken together, these data indicate that sulforaphane activates protein degradation machineries in both the brain and peripheral tissues and may be a therapeutic reagent for Huntington's disease and other intractable disorders. Accumulation of mutant huntingtin (mHtt) protein causes Huntington's disease (HD). Sulforaphane (SFN), a naturally occurring compound, increased proteasome and autophagy activities in vivo and enhanced mHtt turnover and cell survival in HD cell models. SFN-mediated mHtt degradation is mainly through the proteasome pathway. These data suggest that SFN can be a therapeutic reagent for treating HD and other intractable disorders.
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