Fibrillation of α-Lactalbumin: Effect of Crocin and Safranal, Two Natural Small Molecules from Crocus sativus

被引:35
作者
Ebrahim-Habibi, Mohammad-Bagher [1 ]
Amininasab, Mehriar [1 ]
Ebrahim-Habibi, Azadeh [2 ]
Sabbaghian, Marjan [3 ]
Nemat-Gorgani, Mohsen [3 ,4 ]
机构
[1] Univ Tehran, Fac Sci, Dept Cell & Mol Biol, Tehran, Iran
[2] Univ Tehran Med Sci, Shariati Hosp, Endocrinol & Metab Res Ctr, Tehran, Iran
[3] Univ Tehran, Inst Biochem & Biophys, Tehran, Iran
[4] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA
基金
美国国家科学基金会;
关键词
Apo alpha lactalbumin; crocin; safranal; saffron; fibrillation; amyloid; cell toxicity; MOLTEN GLOBULE INTERMEDIATE; PROTEIN MISFOLDING DISEASES; ALZHEIMERS-DISEASE; AMYLOID FIBRILS; IN-VITRO; ALTERNATIVE CONFORMATIONS; THIOFLAVINE-T; AGGREGATION; SAFFRON; MECHANISM;
D O I
10.1002/bip.21477
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
Formation of toxic amyloid structures is believed to be associated with various late-onset neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The fact that many proteins in addition to those that are associated with clinical conditions have the potential to form amyloid fibrils in vitro provides opportunities for studying the fundamentals of protein aggregation and amyloid formation in model systems. Accordingly, considerable interest and effort has been directed toward developing small molecules to inhibit the formation of fibrillar assemblies and their associated toxicities. In the present study, we investigated the inhibitory effect of crocin and safranal, two principal components of saffron, on fibrillation of apo-alpha-lactalbumin (a-alpha-LA), used as a model protein, under amyloidogenic conditions. In the absence of any ligand, formation of soluble oligomers became evident after 18 h of incubation, followed by subsequent appearance of mature fibrils. Upon incubation with crocin or safranal, while transition phase to monomeric beta structures was not significantly affected, formation of soluble oligomers and following fibrillar assemblies were inhibited. While both safranal and crocin had the ability to bind to hydrophobic patches provided in the intermediate structures, and thereby inhibit protein aggregation, crocin was found more effective, possibly due to its simultaneous hydrophobic and hydrophilic character. Cell viability assay indicated that crocin could diminish toxicity while safranal act in reverse order. (C) 2010 Wiley Periodicals, Inc. Biopolymers 93: 854-865, 2010.
引用
收藏
页码:854 / 865
页数:12
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