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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >γ-Carboxyglutamic acid content of hepatocellular carcinoma-associated des-γ-carboxy prothrombin
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γ-Carboxyglutamic acid content of hepatocellular carcinoma-associated des-γ-carboxy prothrombin

机译：肝细胞癌相关的des-γ-羧基凝血酶原的γ-羧基谷氨酸含量

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摘要

Serum des-γ-carboxy prothrombin (DCP) is a useful marker for the diagnosis of hepatocellular carcinoma (HCC), but the exact mechanism of its synthesis and its structural properties in liver diseases are unknown. DCP is measured by the monoclonal antibody MU-3. The purpose of this study was to examine the epitope of MU-3 and to characterize the differences in DCP between HCC and benign liver diseases. The epitope of MU-3 was examined by ELISA using prothrombin Gla domain polypeptides and was determined to be amino acid residues 17-27 of the prothrombin Gla domain, which has four γ-carboxyglutamic acid residues (Gla) at positions 19, 20, 25 and 26. Peptides having a glutamic acid residue (Glu) at these positions reacted strongly to MU-3 but lost reactivity when Glu 19 or 20 was changed to Gla. In the order of γ-carboxylation, MU-3 reacted strongly to DCP containing 0-1 Gla, weakly to 2-4 Gla and not at all to DCP containing more than five Gla. After adsorbing normal prothrombin with barium carbonate, DCP reaction to MU-3 was measured by determining the amount of DCp that was adsorbed by MU-3-coated beads. The proportion of DCP reacting to MU-3 in HCC was 41.0-76.8%, whereas in patients with benign liver diseases, only 0-42.1% reacted to MU-3. These results indicate that DCP variants preferentially synthesized in HCC have less than four Gla, which are restricted to positions 16, 25, 26 and 29, whereas DCP variants in benign liver diseases have more than five Gla.
机译：血清des-γ-羧基凝血酶原（DCP）是诊断肝细胞癌（HCC）的有用标志物，但其合成的确切机理及其在肝脏疾病中的结构特性尚不清楚。 DCP由单克隆抗体MU-3测量。这项研究的目的是检查MU-3的表位并鉴定HCC和良性肝病之间DCP的差异。使用凝血酶原Gla结构域多肽通过ELISA检查MU-3的表位，并确定为凝血酶原Gla结构域的氨基酸残基17-27，其在19、20、25位具有四个γ-羧基谷氨酸残基（Gla）。 26.在这些位置具有谷氨酸残基（Glu）的肽与MU-3强烈反应，但当将Glu 19或20改变为Gla时丧失反应性。按照γ-羧化的顺序，MU-3与含有0-1 Gla的DCP发生强烈反应，与2-4 Gla发生微弱反应，而与含有5个以上Gla的DCP根本不发生反应。用碳酸钡吸附正常凝血酶原后，通过测定被MU-3包被的小珠吸附的DCp的量来测量MU-3的DCP反应。在肝癌中，DCP对MU-3反应的比例为41.0-76.8％，而在肝脏良性疾病患者中，只有0-42.1％对MU-3反应。这些结果表明，在HCC中优先合成的DCP变体具有少于四个Gla，其限于位置16、25、26和29，而良性肝病中的DCP变体具有超过五个Gla。

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