Chk2 deficiency alleviates irradiation-induced taste dysfunction by inhibiting p53-dependent apoptosis
Chk2 deficiency alleviates irradiation-induced taste dysfunction by inhibiting p53-dependent apoptosis
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Chk2 缺陷通过抑制 p53 依赖性细胞凋亡减轻辐射引起的味觉功能障碍
DOI：
10.1111/odi.12822
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发表时间：
2018-07-01
期刊：
影响因子：
3.8
通讯作者：
Shen，Ming
中科院分区：
文献类型：
--
作者：
Yuan，Zhiyao;Ma，Junchi;Shen，Ming
味觉功能障碍是头颈部恶性肿瘤放疗后最常见的并发症之一，它会导致患者食欲下降，生活质量下降。本研究的目的是调查检查点激酶2（Chk 2）缺陷在辐射诱导的味觉功能障碍中的作用。通过生物化学和免疫组织化学方法，比较了Chk 2-缺陷（Chk 2-/-）小鼠和其野生型（WT）同窝仔在照射前和照射后7天和30天的Chk 2-缺陷（Chk 2-/-）小鼠和其野生型（WT）同窝仔之间的Chk 2-缺陷（Chk 2-/-）和潜在信号通路。- 小鼠表现出较少的II型和III型味觉细胞损失，p53，caspase-3和切割的caspase-3的表达较低，凋亡水平较低。Chk 2-/-小鼠味蕾中H2 O2和MDA含量、T-SOD和GSH-Px活性以及SOD 1、SOD 2和8-OHdG的表达与WT小鼠相比无显著差异。结论Chk 2缺陷下调了p53的表达，抑制了细胞凋亡，部分参与了对味觉细胞的辐射防护作用，但没有改变氧化应激水平，抗氧化能力和味蕾中的氧化DNA损伤。
ObjectiveTaste dysfunction is one of the most common complications following radiotherapy, which leads to decreased appetite and life quality of patients suffering from head and neck cancer. The aim of this study was to investigate the role of checkpoint kinase 2 (Chk2) deficiency in irradiation‐induced taste dysfunction.Materials and methodsAlterations in oxidative stress, DNA damage, and potential signaling pathway were compared between Chk2‐deficient (Chk2−/−) mice and their wild‐type (WT) littermates pre‐irradiation and 7 and 30 days postirradiation by biochemistry and immunohistochemistry.ResultsChk2−/−mice showed less loss of type II and type III taste cells, lower expression of p53, caspase‐3, and cleaved caspase‐3, and lower apoptosis levels. However, no significant differences in H2O2and MDA concentrations, T‐SOD and GSH‐Px activities, and expression of SOD1, SOD2, and 8‐OHdG were detected in the taste buds of Chk2−/−mice as compared to those of WT mice.ConclusionChk2 deficiency downregulated the expression of p53 and inhibited cellular apoptosis, partly contributing to the radioprotective effect on taste cells, but did not alter oxidative stress levels, antioxidant ability, and oxidative DNA damage in taste buds.