脂蛋白(a)的酶和化学修饰选择性地改变其赖氨酸结合功能

Jane Hoover-Plow, Pamela Skocir
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引用次数: 7

摘要

脂蛋白(a) [Lp(a)]作为心血管疾病的危险因素的致病性可能取决于其赖氨酸结合位点(LBS),它赋予Lp(a)与低密度脂蛋白不同的独特功能。使用先前描述的两种功能测定法,即lb -Lp(a)免疫测定法和赖氨酸- sepharose bead测定法,测试Lp(a)的生物学相关修饰对LBS活性的改变。在lps -Lp(a)免疫分析中,用脂蛋白脂肪酶、鞘磷脂酶或磷脂酶c修饰后,观察到Lp(a)的LBS活性变化很小。相反,在磷脂酶A2 (PLA2)处理后,Lp(a)的LBS活性显著(p<0.003)增加,这种增加用赖氨酸- sepharose bead试验证实。这种增加取决于PLA2从Lp(a)中释放的脂肪酸。用2,2′-偶氮(2-氨基丙烷)二盐酸(AAPH)氧化Lp(A)后,Lp(A)的LBS活性降低44%,而CuSO4氧化使Lp(A)的LBS活性提高210%。n -乙酰半胱氨酸(NAC)处理降低了Lp(a)的LBS活性(48%),而同型半胱氨酸处理没有(89%)的影响。因此,对磷脂和蛋白质部分的修饰可以改变Lp(a)的lb -活性。这种酶和化学修饰可能导致Lp(a)在人群中LBS功能的变化。
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Enzymatic and chemical modifications of lipoprotein(a) selectively alter its lysine-binding functions

The pathogenicity of lipoprotein(a) [Lp(a)] as a risk factor for cardiovascular disease may depend upon its lysine binding sites (LBS) which impart unique functions to Lp(a) not shared with low density lipoprotein. Biologically relevant modifications of Lp(a) were tested for alterations of LBS activity using two previously described functional assays, a LBS-Lp(a) immunoassay and a lysine–Sepharose bead assay. In the LBS-Lp(a) immunoassay, minimal changes in the LBS activity of Lp(a) were observed after modification with lipoprotein lipase, sphingomyelinase, or phospholipase C. In contrast, a significant (p<0.003) increase in the LBS activity of Lp(a) occurred after phospholipase A2 (PLA2) treatment, and this increase was confirmed using the lysine–Sepharose bead assay. The increase depended upon the release of fatty acids from Lp(a) by PLA2. A decrease in the LBS activity of Lp(a) occurred after oxidation of Lp(a) with 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) (44% decrease), but CuSO4 oxidation increased LBS activity (210%). N-acetylcysteine (NAC) treatment of Lp(a) decreased (48%) LBS activity while homocysteine treatment had no (89%) effect. Thus, modification of phospholipids and protein moieties can alter the LBS-activity of Lp(a). Such enzymatic and chemical modifications may contribute to the variability in LBS function of Lp(a) seen within the population.

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