Protein Chemistry Laboratory, Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
Int J Biol Macromol. 2012 Oct;51(3):291-8. doi: 10.1016/j.ijbiomac.2012.05.021. Epub 2012 May 23.
In the current study both structural alteration and fibrillation of insulin were studied in the presence of homocysteine thiolactone (HCTL). The spectroscopic studies revealed that HCTL increases rate of insulin unfolding, giving rise to the appearance of solvent-exposed hydrophobic regions and induces a transition from α-helix into predominantly β-sheet structures. Thioflavin-T fluorescence studies revealed that HCTL markedly enhanced the quantity of insulin fibril formation in both agitating and non-agitating systems. Also gel electrophoresis results suggest that HCTL accelerates the process of formation of high molecular weight insulin aggregates. Moreover, insulin fibrils obtained in the presence of HCTL and those collected earlier in the pathway of insulin fibrillation displayed improved cytotoxicity against cancer cells. The enhancement of insulin fibril formation with elevated cytotoxic properties as occurred in the presence of HCTL, may suggest this homocysteine derivative as a possible contributing factor in the pathology of insulin fibrils.
在本研究中，研究了同型半胱氨酸硫内酯 (HCTL) 存在下胰岛素的结构改变和纤化。光谱研究表明，HCTL 增加了胰岛素展开的速率，导致暴露于溶剂的疏水区的出现，并诱导从α-螺旋向主要β-折叠结构的转变。硫黄素-T 荧光研究表明，HCTL 显著增强了在搅拌和非搅拌系统中胰岛素纤维形成的数量。此外，凝胶电泳结果表明，HCTL 加速了高分子量胰岛素聚集体的形成过程。此外，在 HCTL 存在下获得的胰岛素纤维和在胰岛素纤维形成途径中更早收集的纤维显示出对癌细胞的细胞毒性增强。在 HCTL 存在下发生的胰岛素纤维形成增强和细胞毒性升高，可能表明这种同型半胱氨酸衍生物是胰岛素纤维病理的一个可能的促成因素。
