Wang Steven S-S, Liu Kuan-Nan, Lee Wen-Hsuan
Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan.
Biophys Chem. 2009 Sep;144(1-2):78-87. doi: 10.1016/j.bpc.2009.06.010. Epub 2009 Jul 4.
At least twenty human proteins can fold abnormally to form pathological deposits that are associated with several degenerative diseases. Despite extensive investigation on amyloid fibrillogenesis, its detailed molecular mechanisms remain unknown. This study is aimed at exploring the inhibitory activity of curcumin against the fibrillation of hen lysozyme. We found that the formation of amyloid fibrils at pH 2.0 in vitro was inhibited by curcumin in a dose-dependent manner. Moreover, quenching analysis confirmed the existence of an interaction between curcumin and lysozyme, and Van't Hoff analysis indicated that the curcumin-lysozyme interaction is predominantly governed by Van Der Waals force or hydrogen bonding. Curcumin was also found to acquire disaggregating ability on preformed lysozyme fibrils. Finally, we observed that curcumin pre-incubated at 25 degrees C for at least 7 days inhibited lysozyme fibrillogenesis better than untreated curcumin and the enhanced inhibition against HEWL fibrillation might be attributed to the presence of dimeric species.
至少有二十种人类蛋白质会异常折叠，形成与多种退行性疾病相关的病理性沉积物。尽管对淀粉样蛋白纤维形成进行了广泛研究，但其详细的分子机制仍然未知。本研究旨在探索姜黄素对鸡溶菌酶纤维化的抑制活性。我们发现，姜黄素在体外对pH 2.0条件下淀粉样纤维的形成具有剂量依赖性抑制作用。此外，猝灭分析证实了姜黄素与溶菌酶之间存在相互作用，范特霍夫分析表明，姜黄素与溶菌酶之间的相互作用主要由范德华力或氢键主导。还发现姜黄素对预先形成的溶菌酶纤维具有解聚能力。最后，我们观察到，在25℃下预孵育至少7天的姜黄素比未处理的姜黄素对溶菌酶纤维化的抑制效果更好，对溶菌酶纤维化增强的抑制作用可能归因于二聚体的存在。
