Reduced Lipid Bilayer Thickness Regulates the Aggregation and Cytotoxicity of Amyloid- β

被引:150
作者
Korshavn, Kyle J. [1 ,2 ]
Satriano, Cristina [4 ]
Lin, Yuxi [5 ]
Zhang, Rongchun [2 ]
Dulchavsky, Mark [3 ]
Bhunia, Anirban [6 ]
Ivanova, Magdalena I. [2 ,3 ]
Lee, Young-Ho [5 ]
La Rosa, Carmelo [4 ]
Lim, Mi Hee [7 ]
Ramamoorthy, Ayyalusamy [1 ,2 ]
机构
[1] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Program Biophys, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA
[4] Univ Catania, Dept Chem Sci, I-95124 Catania, Italy
[5] Osaka Univ, Inst Prot Res, Osaka 5650871, Japan
[6] Bose Inst, Dept Biophys, Kolkata 700009, W Bengal, India
[7] Ulsan Natl Inst Sci & Technol, Dept Chem, Ulsan 44919, South Korea
基金
新加坡国家研究基金会; 美国国家卫生研究院;
关键词
ALZHEIMERS-DISEASE; A-BETA; ALPHA-SYNUCLEIN; MEMBRANE FRAGMENTATION; PHOSPHOLIPID-BILAYERS; PROTEIN AGGREGATION; OXIDATIVE STRESS; FIBRILS; BINDING; STATE;
D O I
10.1074/jbc.M116.764092
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aggregation of amyloid-beta (A beta) on lipid bilayers has been implicated as Amechanism by which A beta exerts its toxicity in Alzheimer's disease (AD). Lipid bilayer thinning has been observed during both oxidative stress and protein aggregation in AD, but whether these pathological modifications of the bilayer correlate withA beta misfolding is unclear. Here, we studied peptide-lipid interactions in synthetic bilayers of the shortchain lipid dilauroyl phosphatidylcholine (DLPC) as Asimplified model for diseased bilayers to determine their impact on A beta aggregate, protofibril, and fibril formation. A beta aggregation and fibril formation in membranes composed of dioleoyl phosphatidylcholine (DOPC) or 1-palmitoyl-2-oleoyl phosphatidylcholine mimicking normal bilayers served as controls. Differences in aggregate formation and stability were monitored by a combination of thioflavin-T fluorescence, circular dichroism, atomic force microscopy, transmission electron microscopy, and NMR. Despite the ability of all three lipid bilayers to catalyze aggregation, DLPC accelerates aggregation at much lower concentrations and prevents the fibrillation of A beta at low micromolar concentrations. DLPC stabilized globular, membrane-associated oligomers, which could disrupt the bilayer integrity. DLPC bilayers also remodeled preformed amyloid fibrils into Apseudo-unfolded, molten globule state, which resembled on-pathway, protofibrillar aggregates. Whereas the stabilized, membrane-associated oligomers were found to be nontoxic, the remodeled species displayed toxicity similar to that of conventionally prepared aggregates. These results provide mechanistic insights into the roles that pathologically thin bilayers may play in A beta aggregation on neuronal bilayers, and pathological lipid oxidation may contribute to A beta misfolding.
引用
收藏
页码:4638 / 4650
页数:13
相关论文
共 80 条
[41]   Molecular Structure of β-Amyloid Fibrils in Alzheimer's Disease Brain Tissue [J].
Lu, Jun-Xia ;
Qiang, Wei ;
Yau, Wai-Ming ;
Schwieters, Charles D. ;
Meredith, Stephen C. ;
Tycko, Robert .
CELL, 2013, 154 (06) :1257-1268
[42]   Evaluation of thermodynamic properties of irreversible protein thermal unfolding measured by DSC [J].
Manetto, GD ;
La Rosa, C ;
Grasso, DM ;
Milardi, D .
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, 2005, 80 (02) :263-270
[43]  
Marsh D., 1990, CRC HDB LIPID BILAYE, P816
[44]   How Do Membranes Initiate Alzheimer's Disease? Formation of Toxic Arnyloid Fibrils by the Amyloid β-Protein on Ganglioside Clusters [J].
Matsuzaki, Katsumi .
ACCOUNTS OF CHEMICAL RESEARCH, 2014, 47 (08) :2397-2404
[45]   Molecular mechanisms of protein aggregation from global fitting of kinetic models [J].
Meisl, Georg ;
Kirkegaard, Julius B. ;
Arosio, Paolo ;
Michaels, Thomas C. T. ;
Vendruscolo, Michele ;
Dobson, Christopher M. ;
Linse, Sara ;
Knowles, Tuomas P. J. .
NATURE PROTOCOLS, 2016, 11 (02) :252-272
[46]   The interaction of amyloid Aβ(1-40) with lipid bilayers and ganglioside as studied by 31P solid-state NMR [J].
Nakazawa, Yasumoto ;
Suzuki, Yu ;
Williamson, Mike P. ;
Saito, Hazime ;
Asakura, Tetsuo .
CHEMISTRY AND PHYSICS OF LIPIDS, 2009, 158 (01) :54-60
[47]   Pathological aspects of lipid peroxidation [J].
Negre-Salvayre, Anne ;
Auge, Nathalie ;
Ayala, Victoria ;
Basaga, Huveyda ;
Boada, Jordi ;
Brenke, Rainer ;
Chapple, Sarah ;
Cohen, Guy ;
Feher, Janos ;
Grune, Tilman ;
Lengyel, Gabriella ;
Mann, Giovanni E. ;
Pamplona, Reinald ;
Poli, Giuseppe ;
Portero-Otin, Manuel ;
Riahi, Yael ;
Salvayre, Robert ;
Sasson, Shlomo ;
Serrano, Jose ;
Shamni, Ofer ;
Siems, Werner ;
Siow, Richard C. M. ;
Wiswedel, Ingrid ;
Zarkovic, Kamelija ;
Zarkovic, Neven .
FREE RADICAL RESEARCH, 2010, 44 (10) :1125-1171
[48]   Biophysical Comparison of Soluble Amyloid-β(1-42) Protofibrils, Oligomers, and Protofilaments [J].
Nichols, Michael R. ;
Colvin, Benjamin A. ;
Hood, Elizabeth A. ;
Paranjape, Geeta S. ;
Osborn, David C. ;
Terrill-Usery, Shana E. .
BIOCHEMISTRY, 2015, 54 (13) :2193-2204
[49]   Thioflavin T-Silent Denaturation Intermediates Support the Main-Chain-Dominated Architecture of Amyloid Fibrils [J].
Noda, Sayaka ;
So, Masatomo ;
Adachi, Masayuki ;
Kardos, Jozsef ;
Akazawa-Ogawa, Yoko ;
Hagihara, Yoshihisa ;
Goto, Yuji .
BIOCHEMISTRY, 2016, 55 (28) :3937-3948
[50]   Multiple Substitutions of Methionine 129 in Human Prion Protein Reveal Its Importance in the Amyloid Fibrillation Pathway [J].
Nystrom, Sofie ;
Mishra, Rajesh ;
Hornemann, Simone ;
Aguzzi, Adriano ;
Nilsson, K. Peter R. ;
Hammarstrom, Per .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (31) :25975-25984