Department of Biochemistry, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, U.P., India.
Department of Biochemistry, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, U.P., India.
Int J Biol Macromol. 2018 Jun;112:306-314. doi: 10.1016/j.ijbiomac.2018.01.188. Epub 2018 Jan 31.
Human serum albumin (HSA) - the most abundant plasma protein plays an important role in the transport of endogenous and exogenous molecules in the body. Its modifications have been implicated in a variety of pathological disorders. We have studied the interaction of HNE with HSA at a molecular level by docking experiment and the results suggest a strong interaction between HNE and HSA. Immunological studies revealed that the circulating auto-antibodies in rheumatoid arthritis (RA) patients have a stronger affinity towards HNE-modified HSA. The HSA isolated from RA patients (RA-HSA) exhibited HNE mediated damage in its secondary and tertiary structure when compared to HSA derived from healthy human subjects (NH-HSA). RA patients presented a significant rise in carbonyls and a considerable decline in free thiol content. Preferential binding of experimentally induced anti-HNE-HSA antibodies to RA-HSA over NH-HSA was observed by ELISA. The results suggest HNE induced structural perturbations in HSA with neoepitopes that generate anti-HNE-HSA antibodies in RA. Hence, HNE-HSA may provide lead towards the development of a biomarker for the disease.
人血清白蛋白（HSA）是血浆中含量最丰富的蛋白质，在体内内源性和外源性分子的转运中发挥着重要作用。其修饰与多种病理紊乱有关。我们通过对接实验研究了 HNE 与 HSA 的分子水平相互作用，结果表明 HNE 与 HSA 之间存在强烈的相互作用。免疫研究表明，类风湿关节炎（RA）患者的循环自身抗体对 HNE 修饰的 HSA 具有更强的亲和力。与来自健康人类受试者的 HSA（NH-HSA）相比，从 RA 患者中分离出的 HSA（RA-HSA）在其二级和三级结构中表现出 HNE 介导的损伤。与健康对照组相比，RA 患者的羰基显著增加，游离巯基含量明显下降。ELISA 观察到实验诱导的抗-HNE-HSA 抗体优先结合 RA-HSA 而不是 NH-HSA。结果表明，HNE 诱导 HSA 结构发生了扰动，产生了针对 RA 的抗-HNE-HSA 抗体的新表位。因此，HNE-HSA 可能为该疾病的生物标志物的开发提供线索。
