Prx1调控PINK1/Parkin介导的线粒体自噬在实验性口腔黏膜癌变中的作用  

Peroxiredoxin 1 regulates PINK1/Parkin-mediated mitophagy in 4NQO-induced oral carcinogenesis

作　　者：路云萍 李玲玉 景新颖 张敏[1] 王敏[1] 葛丽华[1] 杨晶[1] 汤晓飞[1] LU Yunping;LI Ling-yu;JING Xin-ying;ZHANG Min;WANG Min;GE Li-hua;YANG Jing;TANG Xiao-fei(Beijing Institute of Dental Research,Capital Medical University School of Stomatology,Beijing 100050,China)

机构地区：[1]首都医科大学口腔医学院口腔医学研究所,北京100050

出　　处：《北京口腔医学》2021年第1期1-6,共6页Beijing Journal of Stomatology

基　　金：北京市自然科学基金(7192075)。

摘　　要：目的检测口腔黏膜癌变过程中线粒体自噬相关蛋白PINK1、Parkin表达变化及抗氧化蛋白Prx1对其调控作用,探讨Prx1在口腔黏膜癌变中的作用机制。方法利用4NQO化学诱导Prx1^(+/+)和Prx1+/-小鼠舌黏膜癌变模型,采用免疫组织化学染色及Q-PCR方法,检测PINK1、Parkin在小鼠舌正常黏膜、白斑、白斑伴上皮异常增生、鳞癌组织中的表达。结果在Prx1^(+/+)小鼠舌癌变模型中,PINK1、Parkin蛋白及mRNA表达在舌白斑及白斑伴上皮异常增生组织中显著高于正常黏膜及舌癌组织;与Prx1^(+/+)小鼠各组相比,Prx1敲除导致小鼠舌白斑、白斑伴上皮异常增生及舌癌中PINK1蛋白及mRNA表达明显降低;小鼠舌白斑及舌癌组织中Parkin mRNA表达显著升高。结论线粒体自噬参与了口腔黏膜癌变过程;Prx1可能通过调控PINK1/Parkin介导的线粒体自噬在其中发挥重要作用。Objective To examine the expression of PINK1 and Parkin and investigate the regulatory effect of Prx1 on their expression in 4NQO-induced mouse tongue carcinogenesis.Methods 4NQO-induced animal model of tongue mucosa carcinogenesis was established in Prx1^(+/+)and Prx1+/-mice.The expression of PINK1 and Parkin was examined with immunohistochemistry and Q-PCR at the end of 24 weeks.Results Immunohistochemistry and Q-PCR results showed that in the 4NQO-induced Prx1^(+/+)mouse tongue carcinogenesis model,the protein and mRNA expression of PINK1 and Parkin was significantly higher in the tongue leukoplakia tissues than those in normal and tongue cancer tissues.Compared with the Prx1^(+/+)mice,Prx1 knockout significantly reduced PINK1 protein and mRNA expression in tongue leukoplakia,leukoplakia with hyperplasia,and tongue cancer tissues.In addition,the expression of Parkin mRNA in tongue leukoplakia and cancer tissues was significantly increased.Conclusions Mitophagy is involved in oral carcinogenesis and Prx1 may play a key role via regulating PINK1/Parkin-mediated mitophagy in oral cancer progression.

关 键 词：Prx1 线粒体自噬 口腔癌前病变 口腔鳞状细胞癌 

分 类 号：R780.2[医药卫生—口腔医学]