当前位置: X-MOL 学术Biochimie › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
L-Dopa decarboxylase interaction with the major signaling regulator ΡΙ3Κ in tissues and cells of neural and peripheral origin
Biochimie ( IF 3.9 ) Pub Date : 2019-02-20 , DOI: 10.1016/j.biochi.2019.02.009
Alice G. Vassiliou , Maria-Zacharenia Siaterli , Efseveia Frakolaki , Panayiota Gkogkosi , Ioannis Paspaltsis , Theodoros Sklaviadis , Dido Vassilacopoulou , Niki Vassilaki

L-Dopa decarboxylase (DDC) catalyzes the decarboxylation of L-Dopa to dopamine and 5-hydroxytryptophan (5-HTP) to serotonin. Although DDC has been purified from a variety of peripheral organs, including the liver, kidney and pancreas, the physiological significance of the peripherally expressed enzyme is not yet fully understood. DDC has been considered as a potential novel biomarker for various types of cancer, however, the role of DDC in the development of hepatocellular carcinoma (HCC) remains to be evaluated. Phosphatidylinositol 3-kinase (PI3K), on the other hand, has been shown to play a key role in the tumorigenesis, proliferation, metastasis, apoptosis, and angiogenesis of HCC by regulating gene expression. We initially identified the interaction of DDC with PI3K by means of the phage display methodology. This association was further confirmed in human hepatocellular carcinoma cell lines, human embryonic kidney cells, human neuroblastoma cells, as well as mouse brain, by the use of specific antibodies raised against DDC and PI3K. Functional aspects of the above interaction were studied upon treatment with the DDC inhibitor carbidopa and the PI3K inhibitor LY294002. Interestingly, our data demonstrate the expression of the neuronal type DDC mRNA in HCC cells. The present investigation provides new evidence on the possible link of DDC with the PI3K pathway, underlining the biological significance of this complex enzyme.



中文翻译:

L-Dopa脱羧酶与神经和周围来源的组织和细胞中的主要信号调节因子ΡΙ3Κ相互作用

L-Dopa脱羧酶(DDC)催化L-Dopa脱羧成多巴胺,5-羟基色氨酸(5-HTP)脱氢成5-羟色胺。尽管已从包括肝脏,肾脏和胰腺在内的多种外围器官中纯化了DDC,但尚未完全了解外围表达的酶的生理学意义。DDC被认为是各种类型癌症的潜在新生物标记,但是,DDC在肝细胞癌(HCC)发生中的作用尚待评估。另一方面,已显示磷脂酰肌醇3-激酶(PI3K)通过调节基因表达在HCC的肿瘤发生,增殖,转移,凋亡和血管生成中发挥关键作用。我们最初通过噬菌体展示方法鉴定了DDC与PI3K的相互作用。通过使用针对DDC和PI3K的特异性抗体,在人肝细胞癌细胞系,人胚胎肾细胞,人神经母细胞瘤细胞以及小鼠脑中进一步证实了这种联系。在用DDC抑制剂卡比多巴和PI3K抑制剂LY294002处理后,研究了上述相互作用的功能方面。有趣的是,我们的数据证明了HCC细胞中神经元型DDC mRNA的表达。本研究为DDC与PI3K途径的可能联系提供了新的证据,突显了这种复杂酶的生物学意义。在用DDC抑制剂卡比多巴和PI3K抑制剂LY294002处理后,研究了上述相互作用的功能方面。有趣的是,我们的数据证明了HCC细胞中神经元型DDC mRNA的表达。本研究为DDC与PI3K途径的可能联系提供了新的证据,突显了这种复杂酶的生物学意义。在用DDC抑制剂卡比多巴和PI3K抑制剂LY294002处理后,研究了上述相互作用的功能方面。有趣的是,我们的数据证明了HCC细胞中神经元型DDC mRNA的表达。本研究为DDC与PI3K途径的可能联系提供了新的证据,突显了这种复杂酶的生物学意义。

更新日期:2019-02-20
down
wechat
bug