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Amyloid-beta peptide decreases expression and function of glutamate transporters in nervous system cells.
Tong, Huichun; Zhang, Xiuping; Meng, Xingjun; Xu, Pingyi; Zou, Xiaoming; Qu, Shaogang.
Afiliación
  • Tong H; Department of Neurology, The First People's Hospital of Shunde Affiliated to Southern Medical University, Foshan, Guangdong 528300, China; Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
  • Zhang X; Teaching Center of Experimental Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
  • Meng X; Department of Neurology, The First People's Hospital of Shunde Affiliated to Southern Medical University, Foshan, Guangdong 528300, China; Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
  • Xu P; Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510080, China. Electronic address: pingyixujd@163.com.
  • Zou X; Medical Experimental Research Center, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510900, China. Electronic address: 1814925716@qq.com.
  • Qu S; Department of Neurology, The First People's Hospital of Shunde Affiliated to Southern Medical University, Foshan, Guangdong 528300, China; Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: sgq9528@163.com.
Int J Biochem Cell Biol ; 85: 75-84, 2017 04.
Article en En | MEDLINE | ID: mdl-28189841
Glutamate is an essential excitatory neurotransmitter that regulates brain functions, and its activity is tightly regulated by glutamate transporters. Excess glutamate in the synaptic cleft and dysfunction of excitatory amino acid transporters have been shown to be involved in development of Alzheimer's disease, but the precise regulatory mechanism is poorly understood. Using a D-[3H]-aspartic acid uptake assay, we found that Aß1-42 oligomers impaired glutamate uptake in astrocytes and neurons. In astrocytes, this process was accompanied by reduced expression of GLT-1 and GLAST as detected by Western blot and immunocytofluorescence. However, mRNA levels of EAATs detected by qPCR in astrocytes and neurons were not altered, which suggests that this process is post-translational. Co-localization analysis using immunocytofluorescence showed that ubiquitylation of GLT-1 significantly increased. Therefore, we hypothesized that Aß1-42 oligomers-induced endocytosis of astrocytic GLT-1 may be involved in ubiquitylation. In addition, Aß1-42 oligomers enhanced secretion of IL-1ß, TNF-α, and IL-6 into culture supernatant, which may be correlated with an inflammatory response and altered EAATs expression or function in Alzheimer's disease. These findings support the idea that dysregulation of the glutamatergic system may play a significant role in pathogenesis of Alzheimer's disease. Furthermore, enhancing expression or function of EAATs in astrocytes and neurons might be a new therapeutic approach in treatment of Alzheimer's disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación hacia Abajo / Astrocitos / Péptidos beta-Amiloides / Proteínas de Transporte Vesicular de Glutamato Límite: Animals Idioma: En Revista: Int J Biochem Cell Biol Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación hacia Abajo / Astrocitos / Péptidos beta-Amiloides / Proteínas de Transporte Vesicular de Glutamato Límite: Animals Idioma: En Revista: Int J Biochem Cell Biol Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos