1] Center for Translational Medicine, Shanghai Jiao Tong University, Affiliated Sixth People's Hospital, Shanghai 200233, China [2] Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC 28081, USA.
Cell Death Dis. 2013 Oct 3;4(10):e830. doi: 10.1038/cddis.2013.345.
Asymmetric dimethylarginine (ADMA) is synthesized by protein arginine methyltransferases during methylation of protein arginine residues and released into blood upon proteolysis. Higher concentrations of ADMA in blood have been observed in patients with metabolic diseases and certain cancers. However, the role of ADMA in colon cancer has not been well investigated. ADMA serum levels in human patients diagnosed with colon cancer were found to be higher than those present in healthy subjects. ADMA treatment of LoVo cells, a human colon adenocarcinoma cell line, attenuated serum starvation-induced apoptosis and suppressed the activation of the Fas (APO-1/CD95)/JNK (SAPK) (c-Jun N terminal protein kinase/stress-activated protein kinase)pathway. ADMA also suppressed the activation of JNK triggered by death receptor ligand anti-Fas mAb and exogenous C2-ceramide. Moreover, we demonstrated that ADMA pretreatment protected LoVo cells from doxorubicin hydrochloride-induced cell death and activation of the Fas/JNK pathway. In summary, our results suggest that the elevated ADMA in colon cancer patients may contribute to the blocking of apoptosis of cancer cells in response to stress and chemotherapy.
不对称二甲基精氨酸（ADMA）在蛋白质精氨酸残基的甲基化过程中由蛋白精氨酸甲基转移酶合成，并在蛋白水解时释放到血液中。在代谢性疾病和某些癌症患者的血液中观察到更高浓度的 ADMA。然而，ADMA 在结肠癌中的作用尚未得到很好的研究。在被诊断患有结肠癌的人类患者的血清 ADMA 水平被发现高于健康受试者。ADMA 处理人类结肠腺癌细胞系 LoVo 细胞，可减弱血清饥饿诱导的细胞凋亡，并抑制 Fas（APO-1/CD95）/JNK（SAPK）（c-Jun N 末端蛋白激酶/应激激活蛋白激酶）途径的激活。ADMA 还抑制了死亡受体配体抗 Fas mAb 和外源性 C2-神经酰胺触发的 JNK 的激活。此外，我们证明 ADMA 预处理可保护 LoVo 细胞免受盐酸多柔比星诱导的细胞死亡和 Fas/JNK 途径的激活。总之，我们的结果表明，结肠癌患者中升高的 ADMA 可能有助于阻止癌细胞对应激和化疗的凋亡反应。
