کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10738696 | 1046725 | 2011 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The lipid peroxidation products 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote the formation of α-synuclein oligomers with distinct biochemical, morphological, and functional properties
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کلمات کلیدی
AFMDLBHNEMSA4-oxo-2-nonenal - 4-اکسو-2 غیرنال4-hydroxy-2-nonenal - 4-هیدروکسی-2 غیرنالMTT - MTTα-synuclein - α-سینوکلینMultiple-system atrophy - آتروفی چندتاییOligomers - اولیگومرهاLewy bodies - بدن لویThT - بلهParkinson disease - بیماری پارکینسونEnzyme-linked immunosorbent assay - تست الیزاELISA - تست الیزاOxidative stress - تنش اکسیداتیوDementia with Lewy bodies - تهوع و استفراغ با بدن LewyThioflavin T - تیوفلاوین TFree radicals - رادیکال آزادcircular dichroism - رنگ تابی دورانیatomic force microscopy - میکروسکوپ نیروی اتمیLipid peroxidation - پراکسیداسیون لیپیدProteinase K - پروتئیناز KONE - یکم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The lipid peroxidation products 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote the formation of α-synuclein oligomers with distinct biochemical, morphological, and functional properties The lipid peroxidation products 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote the formation of α-synuclein oligomers with distinct biochemical, morphological, and functional properties](/preview/png/10738696.png)
چکیده انگلیسی
Oxidative stress has been implicated in the etiology of neurodegenerative disorders with α-synuclein pathology. Lipid peroxidation products such as 4-oxo-2-nonenal (ONE) and 4-hydroxy-2-nonenal (HNE) can covalently modify and structurally alter proteins. Herein, we have characterized ONE- or HNE-induced α-synuclein oligomers. Our results demonstrate that both oligomers are rich in β-sheet structure and have a molecular weight of about 2000 kDa. Atomic force microscopy analysis revealed that ONE-induced α-synuclein oligomers were relatively amorphous, with a diameter of 40-80 nm and a height of 4-8 nm. In contrast, the HNE-induced α-synuclein oligomers had a protofibril-like morphology with a width of 100-200 nm and a height of 2-4 nm. Furthermore, neither oligomer type polymerized into amyloid-like fibrils despite prolonged incubation. Although more SDS and urea stable, because of a higher degree of cross-linking, ONE-induced α-synuclein oligomers were less compact and more sensitive to proteinase K treatment. Finally, both ONE- and HNE-induced α-synuclein oligomers were cytotoxic when added exogenously to a neuroblastoma cell line, but HNE-induced α-synuclein oligomers were taken up by the cells to a significantly higher degree. Despite nearly identical chemical structures, ONE and HNE induce the formation of off-pathway α-synuclein oligomers with distinct biochemical, morphological, and functional properties.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 50, Issue 3, 1 February 2011, Pages 428-437
Journal: Free Radical Biology and Medicine - Volume 50, Issue 3, 1 February 2011, Pages 428-437
نویسندگان
Thomas Näsström, Therese Fagerqvist, Mikael Barbu, Mikael Karlsson, Fredrik Nikolajeff, Alex Kasrayan, Monica Ekberg, Lars Lannfelt, Martin Ingelsson, Joakim Bergström,