NOD2 agonist murabutide alleviates radiation‐induced injury through DNA damage response pathway mediated by ATR

Abstract

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-domaincontaining 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 γ-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. K E Y W O R D SATR, DNA damage response, ionizing radiation, murabutide, NOD2

Glycyrrhizin ameliorating sterile inflammation induced by low-dose radiation exposure

“…Furthermore, an increase in oxidative stress and a decrease in cell viability was observed after low-dose radiation exposure as well. Therefore, low-dose radiation exposure does not only act as an alarmin but also mediates oxidative stress, similar to what was observed in previous studies conducted on relatively high-dose radiation exposures 26 . Subsequently, HMGB1 levels can be lowered and oxidative stress reduced with GL, a direct inhibitor of HMGB1, that subsequently might allow the preservation of cell viability.…”

Glycyrrhizin Ameliorates Radiation Enteritis in Mice Accompanied by the Regulation of the HMGB1/TLR4 Pathway

“…Furthermore, it must be noted that this preliminary study presented here, lacks an exploration of other important factors that mediate radiation enteritis, such as the destruction of the intestinal epithelial barrier and tight junction after irradiation exposure [12,44]. Besides, irradiation exposure not only acts as a proinflammatory signal [5,45], but also mediates oxidative and nitrative stress to induce the production of ROS and NOS in the small intestine [7,9,46,47]. In addition, GL has been reported to possess anti-oxidant properties in a recent study [48].…”

“…e small intestine is considered to be one of the most sensitive tissues in the abdomen to radiation exposure. After transient radiation exposure, ROS and NOS are immediately generated [5][6][7], which can cause severe cell damage, including DNA damage and the release of intracellular cytokines [8,9]. Radiation-induced DNA damage can act as a damage-associated molecular pattern (DAMP) to stimulate inflammatory responses, as well as destruction of the intestinal epithelial barrier mediated by abdominal radiation exposure, ultimately resulting in radiation enteritis [5,[9][10][11].…”

Analysis of circRNA-miRNA-mRNA Regulatory Network in Peripheral Blood of Radiation Workers

“…At the same time, NOD2 alleviates radiation-induced damage through the agonist of ATR-mediated DNA damage response pathway, Morabutanol, and also inhibits oxidative stress and apoptosis by blocking the participation of wow/ROCK-mediated TAK1/ NOD2 in NF-κB pathway. 28 - 30 Meanwhile, NOD2 also plays an important role in Parkinson’s disease and intestinal disease. 31 , 32 Interferon regulatory factor 7 (IRF7) is highly expressed in the apoptosis of melanoma cell after ultraviolet irradiation, and it is used as a reactive molecular indicator of radiation-induced injury of human umbilical vein endothelial cells.…”