Division of Stem Cell & Gene Therapy Research, Institute of Nuclear Medicine & Allied Sciences (INMAS), Defence Research and Development Organisation (DRDO), Delhi, India.
Int J Radiat Biol. 2020 May;96(5):671-688. doi: 10.1080/09553002.2020.1721592. Epub 2020 Feb 7.
Lithium chloride (LiCl) is clinically used for manic disorders. Its role has been shown in improving cell survival by decreasing Bax and p53 expression and increasing Bcl-2 concentration in the cell. This potential of LiCl is responsible for reducing irradiated cell death. In this study, we have explored the role of LiCl as a radioprotectant affecting survival genes. To find out the cellular response upon LiCl pretreatment to radiation-exposed KG1a cells; viability, clonogenic assay and microarray studies were performed. This was followed by the detection of transcription factor binding motif in coregulated genes. These results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and chromatin immunoprecipitation (CHIP). LiCl improved irradiated KG1a cell survival and its clonogenicity at 2 mM concentration (clinically used). Microarray data analysis showed differential expression of cell-protecting genes playing an important role in apoptosis, cell cycle, adhesion and inflammation, etc. The coregulation analysis revealed genes involved in bile acid biosynthesis were also affected by LiCl treatment, these genes are likely to be responsible for radiation-induced gastrointestinal (GI) syndrome through bile production. This is the first study with respect to global genetic expression upon LiCl treatment to radiation-exposed cells. Our results suggest considering repurposing of LiCl as a protective agent for radiation injury.
氯化锂 (LiCl) 临床上用于治疗躁狂症。研究表明,它通过降低 Bax 和 p53 的表达,增加细胞内 Bcl-2 浓度,从而提高细胞存活率。LiCl 的这种潜力有助于减少辐射导致的细胞死亡。在这项研究中,我们探讨了 LiCl 作为放射保护剂影响存活基因的作用。为了研究 LiCl 预处理对辐射暴露的 KG1a 细胞的细胞反应;进行了细胞活力、集落形成实验和微阵列研究。随后检测了核心调控基因中转录因子结合基序的存在。通过逆转录聚合酶链反应 (RT-PCR) 和染色质免疫沉淀 (CHIP) 对这些结果进行了验证。LiCl 可提高 2 mM 浓度(临床使用)照射的 KG1a 细胞的存活率及其集落形成能力。微阵列数据分析显示,细胞保护基因的差异表达在细胞凋亡、细胞周期、黏附和炎症等方面发挥着重要作用。共调控分析显示,参与胆酸生物合成的基因也受到 LiCl 处理的影响,这些基因可能通过胆汁生成导致辐射诱导的胃肠道 (GI) 综合征。这是第一项关于 LiCl 处理辐射暴露细胞后的全基因组表达的研究。我们的研究结果表明,LiCl 可作为一种辐射损伤的保护剂重新应用。