NOD2 agonist murabutide alleviates radiation-induced injury through DNA damage response pathway mediated by ATR
NOD2 agonist murabutide alleviates radiation-induced injury through DNA damage response pathway mediated by ATR
复制标题
NOD2激动剂村布肽通过ATR介导的DNA损伤反应途径减轻辐射损伤
DOI：
10.1002/jcp.28734
复制
发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Cai, Jianming
中科院分区：
文献类型：
--
作者：
Liu, Lei;Qu, Hongjin;Cai, Jianming
电离辐射(IR)造成的伤害严重降低了受害者的生活质量。发展辐射防护剂被认为是减轻红外辐射损伤的最有效的策略之一。在本研究中，我们研究了nucleotide-binding-oligomerization-domain-containing蛋白2激动剂的辐射防护作用，并阐明了其可能的机制。结果表明，MBD预处理能有效保护培养细胞和小鼠免受IR损伤，体外和体外MBD预处理也能抑制IR诱导的细胞凋亡。MBD可下调γ-H AX的表达，上调ATR信号通路，提示MBD的辐射防护作用是通过刺激DNA损伤反应(DDR)途径修复IR所致的DNA双链断裂而实现的。由于MBD的辐射防护作用被ATR选择性抑制剂而不是ATM抑制剂减弱，ATR通路被证实是介导MBD刺激DDR通路的更关键的检查点通路。综上所述，我们的数据为减轻IR暴露所致的损伤提供了一种新的有效的保护剂。
Injury-induced by ionizing radiation (IR) severely reduces the quality of life of victims. The development of radiation protectors is regarded as one of the most resultful strategies to alleviate damages caused by IR exposure. In the present study, we investigated the radioprotective effects of the agonist of nucleotide-binding-oligomerization-domain-containing proteins 2 called murabutide (MBD) and clarified the potential mechanisms. Our results showed that the pretreatment with MBD effectively protected cultured cells and mice against IR-induced toxicity and the pretreatment with MBD in vitro and in vitro also inhibited apoptosis caused by IR exposure. The downregulation of gamma-H2AX and the upregulation of ATR signaling pathways by MBD treatment indicated that the radioprotective effects of MBD were due to the stimulation of DNA damage response (DDR) pathway to repair DNA double-strand breaks caused by IR exposure. As the radioprotective effects of MBD were diminished by the ATR selective inhibitor rather than the ATM inhibitor, ATR pathway was confirmed to be a more crucial checkpoint pathway in mediating the stimulation of DDR pathway by MBD. Taken together, our data provide a novel and effective protector to relieve the injury induced by IR exposure.