کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5501113 | 1534625 | 2017 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pathological concentration of zinc dramatically accelerates abnormal aggregation of full-length human Tau and thereby significantly increases Tau toxicity in neuronal cells
ترجمه فارسی عنوان
غلظت پاتولوژیک روی به طور قابل توجهی باعث تجمع غیر طبیعی بدن انسان در طول کامل می شود و در نتیجه باعث افزایش سمیت توو در سلول های عصبی
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کلمات کلیدی
IAPPTDP-43GSK-3βDAPIITC3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide - 3- (4،5-dimethylthiazol-2-yl) -2،5-difenyltetrazolium bromideMTT - MTTTHs - THSTem - این استAlzheimer disease - بیماری آلزایمرprotein aggregation - تجمع پروتئینThioflavin S - تیوفلاوین SZinc - فلز رویTransmission electron microscopy - میکروسکوپ الکترونی عبوریPropidium iodide - پروتئین یدیدTau protein - پروتئین تاوIslet amyloid polypeptide - پلی اتیل اتیل آمیلوئیدIsothermal titration calorimetry - کالری سنجی تیتاسیون ایزوترمالGlycogen synthase kinase-3β - گلیکوزین سنتاز کیناز 3β
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
چکیده انگلیسی
A pathological hallmark of Alzheimer disease and other tauopathies is the formation of neurofibrillary tangles mainly composed of bundles of fibrils formed by microtubule-associated protein Tau. Here we study the effects of Zn2Â + on abnormal aggregation and cytotoxicity of a pathological mutant ÎK280 of full-length human Tau. As revealed by Congo red binding assays, transmission electron microscopy, immunofluorescence, Western blot, and immunogold electron microscopy, pathological concentration of Zn2Â + dramatically accelerates the fibrillization of ÎK280 both in vitro and in SH-SY5Y neuroblastoma cells. As evidenced by annexin V-FITC apoptosis detection assay and MTT reduction assay, pathological concentration of Zn2Â + remarkably enhances ÎK280 fibrillization-induced apoptosis and toxicity in SH-SY5Y cells. Substitution of Cys-291 and Cys-322 with Ala, however, essentially eliminates such enhancing effects of Zn2Â + on the fibrillization and the consequent cytotoxicity of ÎK280. Furthermore, Zn2Â + is co-localized with and highly enriched in amyloid fibrils formed by ÎK280 in SH-SY5Y cells. The results from isothermal titration calorimetry show that Zn2Â + binds to full-length human Tau by interacting with Cys-291 and Cys-322, forming a 1:1 Zn2Â +-Tau complex. Our data demonstrate that zinc dramatically accelerates abnormal aggregation of human Tau and significantly increases Tau toxicity in neuronal cells mainly via bridging Cys-291 and Cys-322. Our findings could explain how pathological zinc regulates Tau aggregation and toxicity associated with Alzheimer disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1863, Issue 2, February 2017, Pages 414-427
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1863, Issue 2, February 2017, Pages 414-427
نویسندگان
Ji-Ying Hu, De-Lin Zhang, Xiao-Ling Liu, Xue-Shou Li, Xiao-Qing Cheng, Jie Chen, Hai-Ning Du, Yi Liang,