Fukushima K, Hada T, Higashino K, Yamashita K
Department of Biochemistry, Sasaki Institute, Tokyo, Japan.
Clin Cancer Res. 1998 Nov;4(11):2771-7.
The N-linked sugar chain structures of human hepatic, intestinal, and placental alkaline phosphatases (ALPs) were studied comparatively by chromatography on various lectin columns in combination with digestion by several kinds of exoglycosidases. The sugar chain structures were organ specific. On the basis of these organ-specific structures, we investigated serum ALP using a Neu5Ac(alpha)2-->6Gal(beta)1-->4 GlcNAc-specific Trichosanthes japonica agglutinin-I (TJA-I)-Sepharose column to clarify whether the level of TJA-I-binding serum ALP activity can be used as an indicator to discriminate one form of chronic liver disease from another. Levels of TJA-I-binding ALP in serum were higher in cases of liver cirrhosis and hepatocellular carcinoma than in chronic hepatitis (P < 0.01). The levels of TJA-I-binding ALP in serum did not change significantly after transcatheter arterial embolization, and the amounts of TJA-I-binding ALP activity in noncancerous cirrhotic liver tissues were higher than those in cancerous liver tissues derived from hepatocellular carcinoma patients, indicating that the TJA-I-binding ALP is mainly derived from cirrhotic liver tissues rather than cancerous liver tissues. These results indicate that analysis of the levels of TJA-I-binding ALP in serum is clinically useful for differentiating liver cirrhosis from chronic hepatitis and that altered sugar chain expression in ALP occurs mainly in liver cirrhosis.
通过在各种凝集素柱上进行色谱分析,并结合几种外切糖苷酶的消化作用,对人肝、肠和胎盘碱性磷酸酶(ALP)的N-连接糖链结构进行了比较研究。糖链结构具有器官特异性。基于这些器官特异性结构,我们使用Neu5Ac(α)2→6Gal(β)1→4 GlcNAc特异性的日本栝楼凝集素-I(TJA-I)-琼脂糖柱研究血清碱性磷酸酶,以阐明TJA-I结合血清碱性磷酸酶活性水平是否可用作区分一种慢性肝病与另一种慢性肝病的指标。肝硬化和肝细胞癌患者血清中TJA-I结合碱性磷酸酶水平高于慢性肝炎患者(P<0.01)。经导管动脉栓塞术后,血清中TJA-I结合碱性磷酸酶水平无明显变化,非癌性肝硬化肝组织中TJA-I结合碱性磷酸酶活性高于肝细胞癌患者癌性肝组织中的活性,表明TJA-I结合碱性磷酸酶主要来源于肝硬化肝组织而非癌性肝组织。这些结果表明,分析血清中TJA-I结合碱性磷酸酶水平在临床上有助于区分肝硬化和慢性肝炎,并且碱性磷酸酶中糖链表达的改变主要发生在肝硬化中。