Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Peking University, Beijing, China.
J Gastroenterol Hepatol. 2013 Feb;28(2):365-8. doi: 10.1111/jgh.12043.
Arginine is a nonessential amino acid for humans and mice because it can be synthesized from citrulline by argininosuccinate synthetase (ASS) and argininosuccinate lyase. Hepatocellular carcinoma (HCC) is believed to be auxotrophic for arginine through the lack of expression of ASS. However, there are also some ASS-positive HCC cells. Therefore, the aim of this article was to study the levels of arginine and the expression of ASS in patients with HCC.
Thirty patients with HCC who had undergone HCC surgery were enrolled in the study. Serum arginine levels were determined with an automatic amino acid analyzer. ASS expression was examined by Western blot and immunohistochemistry. Methylation specific polymerase chain reaction and methylation sequencing were performed to detect the methylation of DNA encoding ASS.
There was a decrease of arginine in HCC patients compared with that of healthy control. High expression of ASS was found in the adjacent tissues by Western blot and immunohistochemistry. Little ASS expression was found in most HCC tissues, but there were also some HCC tissues that expressed low levels of ASS. Methylation of the DNA encoding ASS was obviously higher in HCC tissues than that in paired adjacent tissues.
ASS expression is decreased significantly in HCC tissues. The downregulation of arginine and ASS expression may be a self-defense action of the body against malignant tumors, and the decreased arginine and ASS levels in HCC patients are an advantage for the arginine deiminase treatment.
精氨酸是人类和小鼠的非必需氨基酸，因为它可以由瓜氨酸通过精氨琥珀酸合成酶（ASS）和精氨琥珀酸裂解酶合成。肝细胞癌（HCC）被认为通过缺乏 ASS 的表达而对精氨酸具有营养缺陷性。然而，也存在一些 ASS 阳性的 HCC 细胞。因此，本文旨在研究 HCC 患者精氨酸水平和 ASS 的表达。
纳入 30 例接受 HCC 手术的 HCC 患者。采用自动氨基酸分析仪测定血清精氨酸水平。通过 Western blot 和免疫组化检测 ASS 表达。采用甲基化特异性聚合酶链反应和甲基化测序检测编码 ASS 的 DNA 的甲基化。
与健康对照组相比，HCC 患者的精氨酸水平降低。Western blot 和免疫组化显示 ASS 在邻近组织中高表达。大多数 HCC 组织中 ASS 表达水平较低，但也有一些 HCC 组织表达低水平的 ASS。与配对的邻近组织相比，HCC 组织中编码 ASS 的 DNA 甲基化明显更高。
ASS 在 HCC 组织中表达明显下调。精氨酸和 ASS 表达的下调可能是机体对恶性肿瘤的一种自我防御反应，HCC 患者精氨酸和 ASS 水平降低是精氨酸脱氨酶治疗的优势。
