P53 and taurine upregulated gene 1 promotes the repair of the DeoxyriboNucleic Acid damage induced by bupivacaine in murine primary sensory neurons.
P53 and taurine upregulated gene 1 promotes the repair of the DeoxyriboNucleic Acid damage induced by bupivacaine in murine primary sensory neurons.
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DOI：
10.1080/21655979.2022.2048985
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发表时间：
2022-03
期刊：
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
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作者：
本研究旨在探讨P53蛋白和长非编码RNA(LncRNA)牛磺酸上调基因1(TUG1)在布比卡因(BUP)神经毒性中的生物学作用。我们用BUP处理背根神经节细胞，通过CCK-8检测细胞存活率，TUNEL法检测细胞凋亡，γ-H_2AX蛋白和彗星实验检测脱氧核糖核酸损伤，包括通过Q-PCR法和Western印迹法检测P53mRNA、蛋白和TUG1mRNA的表达，并通过沉默P53和TUG1后检测细胞存活率和DNA损伤，并用TUG1FISH结合P53蛋白免疫荧光(IF)来确定这些分子的细胞定位。在体内实验中，我们探讨了鞘内注射BUP对P53基因和蛋白、TUG_1、γ-H_2AX蛋白表达的影响。结果表明，BUP能显著降低细胞存活率，促进细胞凋亡率和DNA损伤，并能增加P53的表达和TUG1的表达。P53 siRNA和TUG1 siRNA显著增加DNA损伤。此外，生物信息学分析和共定位实验表明，P53蛋白是TUG1的转录因子。在体内实验中，鞘内注射BUP后，小鼠背根神经节中P53mRNA、P53蛋白、TUG1和γ-H_2AX蛋白的表达增加。本研究发现P53和TUG1可促进BUP所致小鼠背根神经节细胞DNA损伤的修复，为改善BUP所致的神经毒性提供了新的策略。
The research aimed to explore the biological role of p53 protein and long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in bupivacaine (bup)-induced neurotoxicity. Our work treated dorsal root ganglion (DRG) cells with bup, detected cell viability through CCK-8, apoptosis through TUNEL assays, DeoxyriboNucleic Acid (DNA) damage through γ-H2AX protein and comet assay, including p53 mRNA, protein and TUG1 expression through q-PCR and western blot, furthermore, cell viability and DNA damage were determined after the silencing of p53 and TUG1, biological information and TUG1 FISH combined with p53 protein immunofluorescence (IF) was performed to determine the cellular localization of these molecule. In vivo experiments, we explored the impact of intrathecal injection of bup on p53 mRNA and protein, TUG1, γ-H2AX protein expression. The results showed that bup was available to signally decreased cell viability, promoted apoptosis rate and DNA damage, additionally, bup increased p53 mRNA and protein and TUG1 expression. P53 siRNA and TUG1 siRNA significantly increased DNA damage. Furthermore, bioinformatics analysis and colocalization experiments revealed that the p53 protein is a transcription factor of TUG1, in vivo experiment, intrathecal injection of bup increased the p53 mRNA, p53 protein, TUG1 and γ-H2AX protein in the murine DRG. In this study, it was found p53 and TUG1 promote the repair of the DNA damage induced by bup in murine dorsal root ganglion cells, suggesting a new strategy for the amelioration of bup-induced neurotoxicity.
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影响因子：
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影响因子：
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