原儿茶酸对人血清白蛋白淀粉样纤维化的抑制作用

Inhibitory Effect of Protocatechuic Acid on Human Serum Albumin Amyloid Fibers

以人血清白蛋白为模型,研究了原儿茶酸对蛋白质淀粉样纤维化的抑制作用及抑制机制。采用硫黄素T测定蛋白纤维化过程,结果表明原儿茶酸对蛋白质纤维化的抑制呈现浓度依赖性,当原儿茶酸浓度为250μmol·L^-1和500μmol·L^-1时,其抑制率分别达到了42.5%和59.5%。透射电镜直观地显示出原儿茶酸对蛋白质纤维化的抑制作用。8-苯氨基-1-萘磺酸荧光光谱和圆二色谱分析结果显示,原儿茶酸能够显著地减少纤维化蛋白表面疏水性氨基酸残基的暴露,稳定蛋白质的α螺旋结构。分子模拟结果表明,氢键和疏水作用力驱动原儿茶酸与人血清白蛋白的相互作用,并与赖氨酸残基特异性结合以维持蛋白质构象的稳定,从而达到抑制蛋白纤维化的效果。

The inhibitory effect and mechanism of protocatechuic acid on protein amyloid fibers were studied by using human serum albumin(HSA)as model.Thioflavin T was used to determine the process of protein amyloid fibers.It was found that procatechuic acid inhibited protein amyloid fibers in a dose-dependent manner,when the concentrations of procatechuic acid were 250 and 500μmol·L^-1,the inhibitory rates were 42.5%and 59.5%,respectively.Transmission electron microscopy visually showed the inhibitory effect of protocatechuic acid on protein amyloid fibers.8-Benzene amino-1-naphthalene sulfonic acid fluorescence and circular dichroism spectra results suggested that procatechuic acid could significant decrease the exposure of hydrophobic amino acid residues on the surface of fibrosis protein and stabilize theα-helix structure of protein.Molecular docking results exhibited that the interaction between procatechuic acid and human serum albumin mainly driven by hydrophobic interactions and hydrogen bonding,and the specifical binding of procatechuic acid to lysine residues maintained the conformational stability of the protein,thus inhibiting HSA amyloid fibers.