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首页> 外文期刊>Cellular Physiology and Biochemistry >Cell Death Induced by Uridine 5'-triphosphate (UTP) in Contrast to Adenosine 5'-triphosphate (ATP) in Human Epidermoid Carcinoma Cells (A-431)
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Cell Death Induced by Uridine 5'-triphosphate (UTP) in Contrast to Adenosine 5'-triphosphate (ATP) in Human Epidermoid Carcinoma Cells (A-431)

机译：尿苷5'-三磷酸（UTP）与人表皮样癌细胞（A-431）中的腺苷5'-三磷酸（ATP）相比引起的细胞死亡

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Objective: Extracellular ATP has been reported as an important signaling molecule mediating quite divergent specific biological effects. Recent clinical trials suggest a potential role of ATP in cancer treatment. The aim of our study was to analyze the mechanisms of UTP in comparison to ATP-mediated cell death in an established cell line model (A-431). Methods: Cell culture and proliferation assays, separation of nucleotides by thin-layer technique, measurement of cytosolic free Ca2+, flow cytometry analysis (annexin V), ultra structure, semi-quantitative RT-PCR, standard statistics. Results: ATP, when added as a single dose between 100 and 500 mu M to A-431 cell cultures, showed increasing cytotoxicity, mainly as apoptosis, with a paradoxically decreasing effect at higher concentrations up to 1500 mu M. Doses exceeding 1500 mu M again led to increasing cytotoxicity. UTP at doses between 500 and 3000 mu M resulted in increasing cell death following a normal sigmoid dose-response model. ATP and UTP were degraded by membrane-bound ectoenzymes. ATP degradation products, e. g. adenosine, also induced cell death. Dipyridamole, an adenosine uptake inhibitor, was able to abolish ATP toxicity, which was also counteracted by the addition of uridine. In addition, we found functional and transcriptional evidence for P2 receptors on A-431 cells. Conclusion: Extracellular ATP seems to act via degradation to adenosine and consecutive induction of apoptosis. In contrast, we were not able to demonstrate analogous mechanisms for cell death mediated by extracellular UTP, but were able to provide some evidence of classical ligand-receptor action of uncleaved UTP on A-431 cells.
机译：目的：据报道细胞外ATP是一种重要的信号分子，可介导相当不同的特定生物学效应。最近的临床试验表明，ATP在癌症治疗中具有潜在作用。我们的研究目的是在建立的细胞系模型（A-431）中分析与ATP介导的细胞死亡相比的UTP机制。方法：细胞培养和增殖测定，薄层技术分离核苷酸，胞质游离Ca2 +的测量，流式细胞术分析（annexin V），超结构，半定量RT-PCR，标准统计。结果：当以单剂量在100至500μM之间加入A-431细胞培养液时，ATP表现出增加的细胞毒性，主要是细胞凋亡，在浓度高达1500μM时，其毒性却反而下降。剂量超过1500μM再次导致细胞毒性增加。按照正常的S型剂量反应模型，UTP剂量在500至3000μM之间会导致细胞死亡增加。 ATP和UTP被膜结合的外切酶降解。 ATP降解产物，例如G。腺苷，也可诱导细胞死亡。腺苷摄取抑制剂双嘧达莫能够消除ATP毒性，而尿苷的加入也可以抵消这种毒性。此外，我们发现了A-431细胞上P2受体的功能和转录证据。结论：细胞外ATP似乎是通过降解为腺苷和连续诱导凋亡而发挥作用。相比之下，我们无法证明由细胞外UTP介导的细胞死亡的类似机制，但能够为未切割的UTP对A-431细胞的经典配体-受体作用提供一些证据。

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