کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1317979 976625 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Binding of α-synuclein with Fe(III) and with Fe(II) and biological implications of the resultant complexes
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
پیش نمایش صفحه اول مقاله
Binding of α-synuclein with Fe(III) and with Fe(II) and biological implications of the resultant complexes
چکیده انگلیسی

Parkinson’s disease (PD) is hallmarked by the abnormal intracellular inclusions (Lewy bodies or LBs) in dopaminergic cells. Amyloidogenic protein α-synuclein (α-syn) and iron (including both Fe(III) and Fe(II)) are both found to be present in LBs. The interaction between iron and α-syn might have important biological relevance to PD etiology. Previously, a moderate binding affinity between α-syn and Fe(II) (5.8 × 103 M−1) has been measured, but studies on the binding between α-syn and Fe(III) have not been reported. In this work, electrospray mass spectrometry (ES-MS), cyclic voltammetry (CV), and fluorescence spectroscopy were used to study the binding between α-syn and Fe(II) and the redox property of the resultant α-syn–Fe(II) complex. The complex is of a 1:1 stoichiometry and can be readily oxidized electrochemically and chemically (by O2) to the putative α-syn–Fe(III) complex, with H2O2 as a co-product. The reduction potential was estimated to be 0.025 V vs. Ag/AgCl, which represents a shift by −0.550 V vs. the standard reduction potential of the free Fe(III)/Fe(II) couple. Such a shift allows a binding constant between α-syn and Fe(III), 1.2 × 1013 M−1, to be deduced. Despite the relatively high binding affinity, α-syn–Fe(III) generated from the oxidation of α-syn–Fe(II) still dissociates due to the stronger tendency of Fe(III) to hydrolyze to Fe(OH)3 and/or ferrihydrite gel. The roles of α-syn and its interaction with Fe(III) and/or Fe(II) are discussed in the context of oxidative stress, metal-catalyzed α-syn aggregation, and iron transfer processes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 104, Issue 4, April 2010, Pages 365–370
نویسندگان
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