Agafonova Lyubov E, Zhdanov Dmitry D, Gladilina Yulia A, Shishparenok Anastasia N, Shumyantseva Victoria V
Institute of Biomedical Chemistry, Pogodinskaya St. 10/8, 119121, Moscow, Russia.
Department of Biochemistry, Рeoples' Friendship University of Russia Named After Patrice Lumumba (RUDN University), Miklukho-Maklaya St. 6, 117198, Moscow, Russia.
Heliyon. 2024 Feb 5;10(3):e25602. doi: 10.1016/j.heliyon.2024.e25602. eCollection 2024 Feb 15.
The aim of this work was to develop an electrochemical approach for the analysis of DNA degradation and fragmentation in apoptotic cells. DNA damage is considered one of the major causes of human diseases. We analyzed the cleavage processes of the circular plasmid pTagGFP2-N and calf thymus DNA, which were exposed to restriction endonucleases (the restriction endonucleases BstMC I and AluB I and the nonspecific endonuclease I). Genomic DNA from the leukemia K562 cell line was used as a marker of the early and late (mature) stages of apoptosis. Registration of direct electrochemical oxidation of nucleobases of DNA molecules subjected to restriction endonuclease or apoptosis processes was proposed for the detection of these biochemical events. Label-free differential pulse voltammetry (DPV) has been used to measure endonuclease activities and DNA damage using carbon nanotube-modified electrodes. The present DPV technique provides a promising platform for high-throughput screening of DNA hydrolases and for registering the efficiency of apoptotic processes. DPV comparative analysis of the circular plasmid pTagGFP2-N in its native supercoiled state and plasmids restricted to 4 and 23 parts revealed significant differences in their electrochemical behavior. Electrochemical analysis was fully confirmed by means of traditional methods of DNA analysis and registration of apoptotic process, such as gel electrophoresis and flow cytometry.
这项工作的目的是开发一种电化学方法,用于分析凋亡细胞中的DNA降解和片段化。DNA损伤被认为是人类疾病的主要原因之一。我们分析了环状质粒pTagGFP2-N和小牛胸腺DNA的切割过程,它们被暴露于限制性内切酶(限制性内切酶BstMC I和AluB I以及非特异性内切酶I)。来自白血病K562细胞系的基因组DNA被用作凋亡早期和晚期(成熟)阶段的标志物。提出通过对经历限制性内切酶或凋亡过程的DNA分子的核碱基直接进行电化学氧化的记录来检测这些生化事件。无标记差分脉冲伏安法(DPV)已用于使用碳纳米管修饰电极测量内切酶活性和DNA损伤。当前的DPV技术为DNA水解酶的高通量筛选以及记录凋亡过程的效率提供了一个有前景的平台。对处于天然超螺旋状态的环状质粒pTagGFP2-N以及被切割为4个和23个片段的质粒进行DPV比较分析,发现它们的电化学行为存在显著差异。通过传统的DNA分析方法和凋亡过程记录方法,如凝胶电泳和流式细胞术,充分证实了电化学分析结果。