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The Investigation of the Apoptose Structural Effects and Mechanism in Leukemic Cells of Sirt1 Inhibitor Sirtinol

机译:Sirt1抑制剂Sirtinol白血病细胞凋亡的结构效应及其机制的研究

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Human SIRT1 is an enzyme that deacetylates the p53 tumor suppressor protein. It has been suggested to modulate p53-dependent functions including DNA damage-induced cell death. Sirtuins are nicotinamide adenine dinucleotide dependent class III histone deacetylase proteins that play a crucial role in several cellular processes, including DNA repair, apoptosis, and lifespan. In this study, we investigated the relationship between sirtinols and apoptosis mechanism at leukemic cells. For this, we applied sirtinol to K-562 (chronic myeloid leukemia) and Jurkat (acute T-cell leukemia) cell lines at different diluti ons in cell culture conditions. And Cdna isolated patient RNA samples, after that Caspase3, Bax, Bcl2 expression performed with used qRT-PCR technique and cells were stained by Annexin V method. According to the results of research, we identified that Sirtinol dilutions were increased in both K-562 and Jurkat, while the number of living cells was decreasing, the number of dead cells increased at 50 μM dilution. Sirtinol, an HDAC inhibitor in the direction of these results, has been observed to be a drug that can be effective in the treatment of CML as well as T-ALL.
机译:人SIRT1是一种使p53肿瘤抑制蛋白脱乙酰的酶。已经建议调节包括DNA损伤诱导的细胞死亡在内的p53依赖性功能。 Sirtuins是烟酰胺腺嘌呤二核苷酸依赖性III类组蛋白脱乙酰基酶蛋白,在几种细胞过程中起着关键作用,包括DNA修复,细胞凋亡和寿命。在这项研究中,我们调查了sirtinols与白血病细胞凋亡机制之间的关系。为此,我们在细胞培养条件下,在不同的稀释度下将西地替诺应用于K-562(慢性粒细胞白血病)和Jurkat(急性T细胞白血病)细胞系。然后从Cdna中分离出患者的RNA样品,然后用qRT-PCR技术进行Caspase3,Bax,Bcl2的表达,并用Annexin V法对细胞进行染色。根据研究结果,我们发现在K-562和Jurkat中Sirtinol稀释液均增加,而活细胞数量减少,而在50μM稀释液中死细胞数量增加。在这些结果的方向上,西地替诺是一种HDAC抑制剂,已被观察到是可以有效治疗CML和T-ALL的药物。

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