Proteomic Analysis on Neuroblastoma Cell Line SH-SY5Y Treated with β–Amyloid
| Autor: | Chun-Lun Ni, 倪群倫 |
|---|---|
| Rok vydání: | 2006 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 94 Amyloid is associated with debilitating human ailments including prominently Alzheimer''s disease (AD), Huntington''s disease, Prion-related diseases and possibly cataract formation. A central event in this kind of aging-related neurological diseases such as Alzheimer''s disease is the conformational change from normally circulating soluble amyloid beta peptides (Aβ) into amyloid fibrils, in the form of senile plaques and neurofibrillary tangles respectively. Some neurofibrillary tangles were also shown to consist of hyperphosphorylated tau proteins. Extracellular Aβ accumulation and intracellular tau tangling would stimulate a series of abnormal signaling and response such as disruption of intracellular ion homeostasis, irregular signal transduction and long-term inflammatory response, all progressively leading to neuronal cell death of neurons. Because brain dissections are often available only after patients'' death, sporadic samples obtained usually belong to the diseased state of a very late stage. Generally it is difficult to observe cellular changes in the early stage, which may play a critical role to unravel the mechanism underlying this group of neurological disorders. In this study we have therefore resorted to using the neuroblastoma cell line SH-SY5Y as a model system to study the effects of extracellular Aβ on the protein expression profiles of neuronal cells by a proteomic approach. We treated neuroblastoma cells with Aβ and found some changes in protein and gene expressions as judged by 2D-PAGE and RT-PCR, respectively. Additionally, some proteins modified by phosphorylation were detected by immunoblotting with antibodies against phosphotyrosine. We also found cells transfected for temporary expression of human αB-crystallin or its mutant, αB-crystallin R120G, showed different tolerance to the toxic effects of Aβ. Since AD is concerned with protein misfolding and αB-crystallin is a small heat-shock protein with chaperone activity, this protein might be involved in signal transduction and cell skeleton regulation. Detailed study of αB-crystallin and its role in the pathogenesis of amyloid formation and Alzheimer''s disease is warranted for future studies. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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