کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8270251 | 1534970 | 2014 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hsp27 suppresses the Cu2+-induced amyloidogenicity, redox activity, and cytotoxicity of α-synuclein by metal ion stripping
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Hsp27 suppresses the Cu2+-induced amyloidogenicity, redox activity, and cytotoxicity of α-synuclein by metal ion stripping Hsp27 suppresses the Cu2+-induced amyloidogenicity, redox activity, and cytotoxicity of α-synuclein by metal ion stripping](/preview/png/8270251.png)
چکیده انگلیسی
Aberrant copper homeostasis and oxidative stress have critical roles in several neurodegenerative diseases. Expression of heat-shock protein 27 (Hsp27) is elevated under oxidative stress as well as upon treatment with Cu2+, and elevated levels of Hsp27 are found in the brains of patients with Alzheimer and Parkinson diseases. We demonstrate, using steady-state and time-resolved fluorescence spectroscopy as well as isothermal titration calorimetry studies, that Hsp27 binds Cu2+ with high affinity (Kd ~10â11 M). Treating IMR-32 human neuroblastoma cells with Cu2+ leads to upregulation of endogenous Hsp27. Further, overexpression of Hsp27 in IMR-32 human neuroblastoma cells confers cytoprotection against Cu2+-induced cell death. Hsp27 prevents the deleterious interaction of Cu2+ with α-synuclein, the protein involved in Parkinson disease and synucleinopathies. Hsp27 attenuates Cu2+- or Cu2+-α-synuclein-mediated generation of reactive oxygen species and confers cytoprotection on IMR-32 cells as well as on mouse primary neural precursor cells. Hsp27 prevents Cu2+-ascorbate or Cu2+-α-synuclein-ascorbate treatment-induced increase in mitochondrial superoxide level and mitochondrial disorganization in IMR-32 cells. Hsp27 dislodges the α-synuclein-bound Cu2+ and prevents the Cu2+-mediated amyloidogenesis of α-synuclein. Our findings that Hsp27 binds Cu2+ with high affinity leading to beneficial effects and that Hsp27 can dislodge Cu2+ from α-synuclein, preventing amyloid fibril formation, indicate potential therapeutic strategies for neurodegenerative diseases involving aberrant Cu2+ homeostasis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 72, July 2014, Pages 176-190
Journal: Free Radical Biology and Medicine - Volume 72, July 2014, Pages 176-190
نویسندگان
Abhishek Asthana, Madhuri Bollapalli, Ramakrishna Tangirala, Raman Bakthisaran, Ch. Mohan Rao,