Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma
Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma
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DOI：
10.1016/s0168-8278(00)80122-1
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发表时间：
2000-12-01
影响因子：
25.7
通讯作者：
Mato, JM
中科院分区：
文献类型：
--
作者：
Avila, MA;Berasain, C;Mato, JM
背景/目的：至少50年前就知道人肝硬化时甲硫氨酸代谢发生改变。然而，这种改变的分子基础尚未完全理解。为了更深入地了解这种状况背后的机制，在26个肝病肝脏中检查了甲硫氨酸腺苷转移酶（MAT 1A）、甘氨酸甲基转移酶（GNMT）、甲硫氨酸合酶（MS）、甜菜碱高半胱氨酸甲基转移酶（BHMT）和胱硫醚β-合酶（CBS）的mRNA水平，方法：采用定量RT-PCR方法检测5例肝癌组织和10例正常肝组织中上述基因的表达。结果：与正常肝组织相比，肝硬化组织中MAT 1A、GNMT、BHMT、CBS和MS mRNA的含量明显降低，肝硬化组织中MAT 1A启动子甲基化程度明显增高。HCC组织中也表现出这些enzymes.Conclusions的mRNA水平下降：这些研究结果建立，丰富的主要基因参与蛋氨酸代谢的mRNA在人类肝硬化和HCC显着减少。肝硬化组织中MAT 1A基因启动子的甲基化可能参与了其表达的降低。这些观察结果有助于解释肝硬化中观察到的高蛋氨酸血症、高同型半胱氨酸血症和肝谷胱甘肽含量减少。
Background/Aims: It has been known for at least 50 years that alterations in methionine metabolism occur in human liver cirrhosis. However, the molecular basis of this alteration is not completely understood, In order to gain more insight into the mechanisms behind this condition, mRNA levels of methionine adenosyl-transferase (MAT1A), glycine methyltransferase (GNMT), methionine synthase (MS), betaine homocysteine methyltransferase (BHMT) and cystathionine beta -synthase (CBS) were examined in 26 cirrhotic livers, five hepatocellular carcinoma (HCC) tissues and ten control livers.Methods: The expression of the above-mentioned genes was determined by quantitative RT-PCR analysis. Methylation of MAT1A promoter was assessed by methylation-sensitive restriction enzyme digestion of genomic DNA.Results: When compared to normal livers MAT1A, GNMT BHMT, CBS and MS mRNA contents were significantly reduced in liver cirrhosis, Interestingly, MAT1A promoter was hypermethylated in the cirrhotic liver. HCC tissues also showed decreased mRNA levels of these enzymes.Conclusions: These findings establish that the abundance of the mRNA of the main genes involved in methionine metabolism is markedly reduced in human cirrhosis and HCC. Hypermethylation of MAT1A promoter could participate in its reduced expression in cirrhosis. These observations help to explain the hypermethioninemia, hyperhomocysteinemia and reduced hepatic glutathione content observed in cirrhosis.