King Saud University, Department of Food Science and Nutrition, Faculty of Food and Agricultural Sciences, 2460, Riyadh 11451, Saudi Arabia.
King Saud University, Department of Biochemistry, College of Science, Riyadh 11451, Saudi Arabia.
Int J Biol Macromol. 2020 Apr 1;148:880-886. doi: 10.1016/j.ijbiomac.2020.01.215. Epub 2020 Jan 23.
Amyloid fibril formation by proteins and their deposition in cells and tissues are associated with several amyloid-based disorders. Understanding the mechanism of amyloid fibril formation is thus of the utmost importance for the designing ligands that could prevent or inhibit the fibrillation process and help to treat of such disorders. We describe the stimulatory effect of sodium dodecyl benzenesulfonate (SDBS) on insulin amyloid fibrillation at pH 2.0 and the characterization of SDBS-induced insulin aggregation using spectroscopy and microscopy. We found that SDBS induced amyloid-like aggregates of insulin at sub-micellar (0.1-1.2 mM), but not post-micellar (≥2.0 mM) concentrations. The amyloid fibrillation of insulin induced by SDBS was kinetically rapid and escaped the lag phase. Far-UV CD findings suggested that the α-helical content of insulin transformed into cross-β structure and mixed α and β structures when incubated with sub-micellar and post-micellar SDBS concentrations, respectively. The overall results indicated that low, but not high SDBS concentrations induce amyloid-like insulin aggregates and fibrils.
蛋白质的淀粉样原纤维形成及其在细胞和组织中的沉积与几种基于淀粉样的疾病有关。因此，了解淀粉样原纤维形成的机制对于设计可以预防或抑制纤维化过程的配体以及帮助治疗这些疾病至关重要。我们描述了十二烷基苯磺酸钠（SDBS）在 pH 2.0 下对胰岛素淀粉样纤维形成的刺激作用，并使用光谱学和显微镜对 SDBS 诱导的胰岛素聚集进行了表征。我们发现，SDBS 在亚胶束（0.1-1.2 mM）浓度下诱导胰岛素形成类似淀粉样的聚集物，但不在胶束后（≥2.0 mM）浓度下。SDBS 诱导的胰岛素淀粉样纤维形成的动力学非常快，并且避开了滞后阶段。远紫外 CD 研究结果表明，当用亚胶束和胶束后 SDBS 浓度孵育时，胰岛素的α-螺旋含量分别转化为交叉-β结构和混合的α和β结构。总的来说，结果表明低浓度而非高浓度的 SDBS 诱导形成类似淀粉样的胰岛素聚集物和纤维。
