Superoxide dismutase 2 (SOD2) is a key enzyme for scavenging reactive oxygen species produced by mitochondria, which plays an important role in maintaining cellular homeostasis. However, its effects on the detoxification capability of liver cells have not been reported. In this study, we found that change in SOD2 expression affects the proliferation of liver cells. Genome-wide microarray analysis showed that SOD2 positively regulates the drug transporter ABCC2, and co-expression analysis suggested that lncRNA CLCA3P participates in the process. Further experiments showed that SOD2 can promote the expression of CLCA3P, which increases the transcription of ABCC2 by interacting with the transcription factor IRF1. By increasing ABCC2 expression SOD2 facilitates drugs efflux of liver cells and thus promotes their survival under a drug-toxic environment. This study elucidates the improvement of the detoxification of liver cells by a regulatory axis, SOD2-CLCA3P-IRF1-ABCC2, and provides novel insight into the modification of human liver cells that can be applied to bioartificial liver system or the study of SOD2 in drug metabolism.

中文翻译：

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SOD2通过lncRNA CLCA3p促进ABCC2的表达，提高肝细胞的解毒能力

超氧化物歧化酶2（SOD2）是清除线粒体产生的活性氧的关键酶，在维持细胞稳态中发挥着重要作用。但其对肝细胞解毒能力的影响尚未见报道。在这项研究中，我们发现SOD2表达的变化会影响肝细胞的增殖。全基因组微阵列分析表明，SOD2 正向调节药物转运蛋白 ABCC2，共表达分析表明 lncRNA CLCA3P 参与了该过程。进一步的实验表明，SOD2可以促进CLCA3P的表达，CLCA3P通过与转录因子IRF1相互作用来增加ABCC2的转录。通过增加 ABCC2 表达，SOD2 促进肝细胞的药物流出，从而促进其在药物毒性环境下的存活。本研究阐明了调节轴SOD2-CLCA3P-IRF1-ABCC2对肝细胞解毒能力的改善，并为人类肝细胞的修饰提供了新的见解，可应用于生物人工肝系统或SOD2在药物中的研究代谢。