Vanillin is a natural compound endowed with antioxidant and anti-mutagenic properties. We previously identified the vanillin derivative VND3207 with strong radio-protective and antioxidant effects and found that VND3207 confers survival benefit and protection against radiation-induced intestinal injury (RIII) in mice. We also observed that VND3207 treatment enhanced the expression level of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) in human lymphoblastoid cells with or without γ-irradiation. DNA-PKcs is a critical component of DNA double strand break repair pathway and also regulates mitotic progression by stabilizing spindle formation and preventing mitotic catastrophe in response to DNA damage. In the present study, we found that VND3207 protected intestinal epithelial cells in vitro against ionizing radiation by promoting cell proliferation and inhibiting cell apoptosis. In addition, VND3207 promoted DNA-PKcs activity by increasing autophosphorylation at S2056 site. Consistent with this, VND3207 significantly decreased the number of γH2AX foci and mitotic catastrophe after radiation. DNA-PKcs deficiency abolished these VND3207 radio-protective effects, indicating that DNA-PKcs activation is essential for VND3207 activity. In conclusion, VND3207 promoted intestinal repair following radiation injury by regulating the DNA-PKcs pathway.

中文翻译：

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香兰素衍生物VND3207激活DNA-PKcs，在体内外对辐射诱导的肠上皮细胞损伤提供保护。

香兰素是一种天然化合物，具有抗氧化剂和抗诱变特性。我们先前鉴定出香兰素衍生物VND3207具有强的辐射防护和抗氧化作用，并发现VND3207赋予小鼠生存优势和对辐射诱发的肠道损伤（RIII）的保护作用。我们还观察到，VND3207处理可在有或没有γ辐射的人淋巴母细胞中提高DNA依赖性蛋白激酶（DNA-PKcs）催化亚基的表达水平。DNA-PKcs是DNA双链断裂修复途径的关键组成部分，还通过稳定纺锤体形成和防止对DNA损伤的有丝分裂灾难来调节有丝分裂的进程。在目前的研究中，我们发现，VND3207通过促进细胞增殖和抑制细胞凋亡，在体外保护肠上皮细胞免受电离辐射。另外，VND3207通过增加S2056位点的自磷酸化来促进DNA-PKcs活性。与此相一致，VND3207显着减少了辐射后γH2AX病灶的数量和有丝分裂灾难。DNA-PKcs的缺乏消除了这些VND3207的放射防护作用，表明DNA-PKcs的激活对于VND3207的活性至关重要。总之，VND3207通过调节DNA-PKcs途径促进了放射损伤后的肠道修复。VND3207显着减少了辐射后γH2AX灶的数量和有丝分裂灾难。DNA-PKcs的缺乏消除了这些VND3207的放射防护作用，表明DNA-PKcs的激活对于VND3207的活性至关重要。总之，VND3207通过调节DNA-PKcs途径促进了放射损伤后的肠道修复。VND3207显着减少了辐射后γH2AX灶的数量和有丝分裂灾难。DNA-PKcs的缺乏消除了这些VND3207的放射防护作用，表明DNA-PKcs的激活对于VND3207的活性至关重要。总之，VND3207通过调节DNA-PKcs途径促进了放射损伤后的肠道修复。