Rizvi Asim, Furkan Mohd, Naseem Imrana
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202 002, India.
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202 002, India.
Arch Biochem Biophys. 2017 Dec 15;636:71-78. doi: 10.1016/j.abb.2017.11.001. Epub 2017 Nov 6.
Malignancies are characterized by several drastic metabolic changes, one of which is a progressive rise in the levels of serum copper. This rise in serum copper is documented across all malignancies and across malignancies in several species. This study aims to explore in vitro the effect of increased copper levels on the structure of the blood protein human serum albumin. Exposure of human serum albumin to physiologically relevant copper concentrations for 21 days resulted in structural modifications in the protein which were evident by changes in the intrinsic florescence. A loss of the predominantly alpha helical structure of human serum albumin was recorded along with a tendency to form protein aggregates. This aggregation was characterized by Thioflavin T and Congo Red assays. Rayleigh light scattering and turbidity assays confirmed aggregation. The aggregates were visually confirmed using transmission electron microscopy. This is the first report implicating increased copper levels as a cause of aggregation of blood proteins in malignancies. The physiological and biochemical implications of this phenomenon are discussed.
恶性肿瘤具有多种显著的代谢变化，其中之一是血清铜水平的逐渐升高。血清铜的这种升高在所有恶性肿瘤以及多个物种的恶性肿瘤中都有记录。本研究旨在体外探究铜水平升高对血液蛋白人血清白蛋白结构的影响。将人血清白蛋白暴露于生理相关的铜浓度下21天，导致蛋白质发生结构修饰，这通过内在荧光的变化得以明显体现。记录到人血清白蛋白主要的α螺旋结构丧失，同时有形成蛋白质聚集体的倾向。这种聚集通过硫黄素T和刚果红测定法进行表征。瑞利光散射和浊度测定法证实了聚集。使用透射电子显微镜在视觉上确认了聚集体。这是第一份将铜水平升高牵连为恶性肿瘤中血液蛋白聚集原因的报告。讨论了这一现象的生理和生化意义。
