Wang Steven S-S, Liu Kuan-Nan, Han Tzu-Chiang
Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan.
Biochim Biophys Acta. 2010 Jun;1802(6):519-30. doi: 10.1016/j.bbadis.2010.02.008. Epub 2010 Feb 20.
Amyloid fibrils have been associated with at least 25 different degenerative diseases. The 51-residue polypeptide hormone insulin, which is associated with type II diabetes, has been shown to self-assemble to form amyloid fibrils in vitro. With bovine insulin as a model, the research presented here explores the effects of two amphiphilic surfactants (1,2-dihexanoyl-sn-glycero-3-phosphocholine (di-C7-PC) and 1,2-diheptanoyl-sn-glycero-3-phosphocholine (di-C7-PC)) on the in vitro fibrillation process of bovine insulin at pH 2.0 and 55 degrees C. We demonstrated that insulin fibrillation may be inhibited by both surfactants in a dose-dependent fashion. The best inhibition of fibril formation is observed when insulin is incubated with 4mM di-C7-PC. Moreover, the addition of either surfactant at the concentrations studied attenuated insulin fibril-induced cytotoxicity in both PC12 and SH-SY5Y cell lines. The results from this work may contribute to the understanding of the molecular factors affecting amyloid fibrillation and the molecular mechanism(s) of the interactions between the membrane and amyloid proteins.
淀粉样纤维已与至少25种不同的退行性疾病相关联。与II型糖尿病相关的由51个氨基酸残基组成的多肽激素胰岛素，已被证明在体外能自组装形成淀粉样纤维。以牛胰岛素为模型，本文的研究探讨了两种两亲性表面活性剂（1,2 - 二己酰基 - sn - 甘油 - 3 - 磷酸胆碱（二 - C7 - PC）和1,2 - 二庚酰基 - sn - 甘油 - 3 - 磷酸胆碱（二 - C7 - PC））在pH 2.0和55摄氏度条件下对牛胰岛素体外纤维化过程的影响。我们证明，两种表面活性剂均能以剂量依赖的方式抑制胰岛素纤维化。当胰岛素与4mM二 - C7 - PC孵育时，观察到对纤维形成的最佳抑制效果。此外，在所研究的浓度下添加任何一种表面活性剂，均可减轻胰岛素纤维在PC12和SH - SY5Y细胞系中诱导的细胞毒性。这项工作的结果可能有助于理解影响淀粉样纤维化的分子因素以及膜与淀粉样蛋白之间相互作用的分子机制。
