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Pharmaceutical acetylation can modulate the amyloidogenicity of human serum albumin
Indian Journal of Biochemistry and Biophysics ( IF 1.5 ) Pub Date : 2021-07-30
Vidhya Bharathi, Ruchi Rajkumar Manglunia, Neetu Sharma, Sadhana Nirwal, Basant K Patel

Human serum albumin (HSA) is an abundant carrier protein present in the blood plasma manifesting affinity for drugs and ligands. The bindings of several drugs can cause changes in the structural conformation of HSA that may affect its function. HSA is also known to in vitro form amyloid-like aggregates with fibrillar morphology as observed under TEM. Earlier, we showed that the HSA amyloid-like aggregates display self-seeding potential and detergent stability and the dimers of HSA, which are preferable for clinical applications due to their longer circulatory life, can also form amyloid-like aggregates. As aspirin, a commonly prescribed drug, was previously documented to acetylate HSA at one of its lysine residues, here, we examined if acetylation has any effect on the in vitro amyloid-like aggregation of HSA. We show that HSA acetylated in vitro using acetylsalicylic acid manifests relatively reduced levels of amyloid-specific properties such as turbidity, Thioflavin-T-positive aggregation, -sheet content and stability against an ionic detergent. Also, TEM imaging shows that the acetylated HSA forms relatively less aggregates and with smaller sizes whereas, the aggregates of HSA are more abundant and larger in sizes with fibrillar morphology which further supports that acetylation can attenuate the amyloid-like aggregation of HSA.

中文翻译:

药物乙酰化可调节人血清白蛋白的淀粉样变性

人血清白蛋白 (HSA) 是血浆中存在的一种丰富的载体蛋白,对药物和配体具有亲和力。几种药物的结合会导致 HSA 结构构象的变化,这可能会影响其功能。还已知 HSA 在体外形成具有纤维形态的淀粉样聚集体,如在 TEM 下观察到的。早些时候,我们表明 HSA 淀粉样聚集体显示出自播种潜力和洗涤剂稳定性,并且 HSA 的二聚体由于其更长的循环寿命而更适合临床应用,也可以形成淀粉样聚集体。由于阿司匹林是一种常用处方药,之前有记载可将 HSA 的一个赖氨酸残基乙酰化,因此,我们在这里检查了乙酰化是否对 HSA 的体外淀粉样蛋白样聚集有任何影响。我们表明,使用乙酰水杨酸在体外乙酰化的 HSA 表现出相对降低的淀粉样蛋白特异性特性水平,例如浊度、硫磺素-T 阳性聚集、-片层含量和对离子去污剂的稳定性。此外,TEM 成像显示乙酰化 HSA 形成的聚集体相对较少,尺寸更小,而 HSA 的聚集体更丰富,尺寸更大,具有纤维状形态,进一步支持乙酰化​​可以减弱 HSA 的淀粉样蛋白聚集。
更新日期:2021-07-30
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