Haptoglobin次單元在其生物功能上所扮演之角色

Abstract

當組織受到損傷或是受到感染時，受損的部位便開使產生發炎反應，而急性期血漿蛋白(APPs)開始大量表現。Haptoglobin(Hp)是主要的急性期血漿蛋白之一。Hp有許多重要的生物功能，例如:能與血紅素(hemoglobin)結合、且具有抗氧化、抗發炎能力與促使血管新生。而這些重要的生物功能中又以與血紅素結合與抗氧化能力最為重要。當動脈發生溶血時，氧化壓力(oxidative stress)會引起低密度脂蛋白(LDL)氧化與造成血管內皮損害。被氧化的低密度脂蛋白，會被巨噬細胞(macrophage)透過特殊的接受器清除，之後會進入血管內壁堆積，造成血管堵塞而形成動脈硬化。Hp藉著能與血紅素結合與抗氧化的能力能夠防止動脈硬化的形成， 因此，在動脈硬化扮演一個很重要的角色。 Hp是由α與β次單元所組成之急性期蛋白，而本篇研究主要探討那一個次單元是主要提供Hp重要的功能。因為Hp的次單元之間，主要是藉由双硫鍵鍵結，而透過還原後，通過凝膠過濾管柱法(gel-filtration column)將α與β次單元分離純化，得到了兩個次單元後，開始針對Hp的功能做研究。在Hp之功能與結構上，例如:醣基之修飾、二級結構之組成及與Hb結合能力實驗證實β次單元是主要提供Hp結構與生物功能。不過，在血管新生及抗氧化能力的部分， α與β兩次單元都扮演著非常重要的角色，因為這兩個次單元都能促使血管新生及具有抗氧化之能力。

Sterile tissue injury or infection initiates a local inflammatory response that mobilizes a systemic acute phase plasma proteins (APPs). Haptoglobin (Hp), one of the major APPs, has many important functions. A number of biological functions of Hp have been evaluated, such as high-affinity hemoglobin binding activity, antioxidant property, anti-inflammatory property, and angiogenesis. These functions of Hp are very important, especially hemoglobin binding activity and antioxidant property. While hemolysis occurs in the artery, the oxidative stress will be elevated to promote the initiation of LDL oxidation and destruction of vascular endothelium. Following the internalization of oxidative LDL particles in macrophages through specific scavenger receptors, the accumulation of oxidized LDL initiates the formation of atherosclerosis. Therefore, Hp may serve as an important role in prevention of atherosclerosis due to its potent antioxidant property. Hp is an acute phase protein which is composed of α and β subunits. The purpose of this study is to explore and evaluate what subunits contribute functions of Hp. The disulfide-linked cysteines of Hp were first reduced followed by gel-filtration chromatography to isolate α and β subunits. With respect to biological function of Hp, β subunit contributed the greater part of functions of Hp. According to this result, many functions of Hp were offered by β subunit.