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Peroxynitrite-induced conformational changes in DNA that lead to cell death: UV, CD spectral, molecular dynamics simulation and FACS analysis
Nucleosides, Nucleotides & Nucleic Acids ( IF 1.1 ) Pub Date : 2020-09-15 , DOI: 10.1080/15257770.2020.1809673
G Anushree 1 , P Aravind 2 , D Vinod 3 , N Hemalatha 4, 5 , S T Girisha 2 , K S Devaraju 1, 2
Affiliation  

Abstract Peroxynitrite is known to react with biomolecules leading to their structural and function alteration. Structural alteration in DNA induced by peroxynitrite is not clearly known. The current study was carried out to decipher the changes induced by peroxynitrite using UV-Vis spectra, circular dichrometry, molecular dynamics simulation followed by restriction digestion. Apoptotic markers Bax, Bcl-2 and caspase genes were also studied by FACS in peroxynitrite induced PC12 cells. The results obtained showed that PXN binds to DNA leading to hyperchromicity of DNA in the presence of PXN over a period of time and the same was established by In silico studies where PXN modifies the DNA to accommodate itself into the stacking and brings about the significant structural alterations. Further, FACS studies reveal that Bcl-2 gene expression was down regulated whereas BAXand caspase genes were up regulated compared to control concluding that PXN induces apoptotic cell death in PC12 cells

中文翻译:

过氧亚硝酸盐诱导的 DNA 构象变化导致细胞死亡:UV、CD 光谱、分子动力学模拟和 FACS 分析

摘要 众所周知,过氧亚硝酸盐会与生物分子发生反应,导致其结构和功能发生改变。过氧亚硝酸盐引起的 DNA 结构改变尚不清楚。目前的研究是使用 UV-Vis 光谱、圆二色法、分子动力学模拟和限制性消化来破译过氧亚硝酸盐引起的变化。还通过 FACS 在过氧亚硝酸盐诱导的 PC12 细胞中研究了凋亡标志物 Bax、Bcl-2 和 caspase 基因。获得的结果表明 PXN 与 DNA 结合导致 DNA 在 PXN 存在下经过一段时间的增色性,并且通过计算机研究证实了这一点,其中 PXN 修饰 DNA 以使其自身适应堆积并带来显着的结构改动。更多,
更新日期:2020-09-15
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