Peroxiredoxin 1 suppresses apoptosis via regulation of the apoptosis signal-regulating kinase 1 signaling pathway in human oral leukoplakia.
Peroxiredoxin 1 suppresses apoptosis via regulation of the apoptosis signal-regulating kinase 1 signaling pathway in human oral leukoplakia.
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DOI：
10.3892/ol.2015.3424
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发表时间：
2015-09
期刊：
影响因子：
2.9
通讯作者：
Min Zhang;Wenwen Niu;Jianfei Zhang;L. Ge;Jing Yang;Zheng Sun;Xiaofei Tang
中科院分区：
文献类型：
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作者：
Min Zhang;Wenwen Niu;Jianfei Zhang;L. Ge;Jing Yang;Zheng Sun;Xiaofei Tang
过氧化还蛋白1(PRX1)在多种恶性肿瘤中起重要作用。然而，PRX1在口腔白斑(OLK)中的作用尚不清楚。口腔白斑是口腔黏膜常见的癌前病变，恶变率很高。本研究旨在探讨PRX1在OLK中的作用及其与凋亡信号调节蛋白1(ASK1)和p38的关系。20例口腔白斑标本和10例正常口腔黏膜标本均取自北京口腔医院(北京，中国)。用聚合酶链式反应和免疫印迹法分别检测PRX1、ASK1和p38的信使RNA(MRNA)和蛋白表达水平。流式细胞仪检测细胞凋亡率。用谷胱甘肽-S-转移酶下拉试验和免疫共沉淀法研究了过氧化氢处理的DOK细胞中Prx1和ASK1的相互作用。与正常口腔黏膜相比，口腔白斑组织中PRX1、ASK1和p38基因的表达水平显著升高(P<；0.05)。OLK组织中PRX1、p-ASK1和p-p38的蛋白表达水平也显著高于正常组织(P<；0.05)。在PRX1基因敲除的DOK细胞中，ASK1和p38被激活，导致对过氧化氢的反应增加了细胞凋亡水平。在经过氧化氢处理的DOK细胞中，未检测到PRX1和ASK1之间明显的相互作用。PRX1可能通过抑制ASK1诱导的细胞凋亡信号通路来抵抗细胞外氧化应激损伤，从而参与OLK的发病。靶向PRX1可能为治疗OLK患者提供一种新的治疗策略。
Peroxiredoxin 1 (Prx1) has a significant role in several malignant types of tumor. However, the role of Prx1 in oral leukoplakia (OLK) has remained to be elucidated. OLK is a common precancerous lesion of the oral mucosa that has a very high malignant transformation rate. The aim of the present study was to investigate the roles of Prx1, and its association with apoptosis signal-regulating kinase 1 (ASK1) and p38 in OLK. A total of 20 OLK samples and 10 normal oral mucosa samples were obtained from patients at the Beijing Stomatological Hospital (Beijing, China). The messenger RNA (mRNA) and protein expression levels of Prx1, ASK1 and p38 were determined by polymerase chain reaction and western blot analysis, respectively. Flow cytometry was used to detect cell apoptosis. The interaction between Prx1 and ASK1 was examined in H2O2-treated DOK cells by glutathione-S-transferase pull-down assays and by co-immunoprecipitation in vitro. Compared with those of the normal oral mucosa, the mRNA levels of Prx1, ASK1 and p38 were elevated in OLK tissues (P<0.05). The protein expression levels of Prx1, phosphorylated-ASK1 (p-ASK1) and p-p38 were also significantly enhanced in OLK tissues compared with those of the normal mucosa (P<0.05). In Prx1-knockdown DOK cells, ASK1 and p38 were activated, leading to enhanced levels of apoptosis in response to H2O2. No clear interaction between Prx1 and ASK1 was detected in H2O2-treated DOK cells. Prx1 was suggested to be involved in OLK pathogenesis by providing resistance against extracellular damages from oxidative stress via inhibition of the ASK1-induced apoptotic signaling pathway. Targeting Prx1 may provide a novel therapeutic strategy for the treatment of patients with OLK.