Peroxiredoxin 1 has an anti-apoptotic role via apoptosis signal-regulating kinase 1 and p38 activation in mouse models with oral precancerous lesions

Zhang,Jianfei; Jing,Xinying; Niu,Wenwen; Zhang,Min; Ge,Lihua; Miao,Congcong; Tang,Xiaofei

doi:10.3892/ol.2016.4659

Peroxiredoxin 1 has an anti-apoptotic role via apoptosis signal-regulating kinase 1 and p38 activation in mouse models with oral precancerous lesions

Authors:
- Jianfei Zhang
- Xinying Jing
- Wenwen Niu
- Min Zhang
- Lihua Ge
- Congcong Miao
- Xiaofei Tang
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Affiliations: Beijing Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Beijing Key Laboratory, Capital Medical University, Beijing 100050, P.R. China
Published online on: June 1, 2016 https://doi.org/10.3892/ol.2016.4659
Pages: 413-420

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Abstract

Peroxiredoxin 1 (Prx1) is important in the protection of cells from oxidative damage and the regulation of cell proliferation and apoptosis. Prx1 is overexpressed in oral precancerous lesions of oral leukoplakia (OLK) and oral cancer; however, the association between Prx1 expression and OLK pathogenesis remains unknown. The present study investigated the role of Prx1 and its molecular mechanisms in oxidative stress‑induced apoptosis during the pathogenesis of OLK. Wild‑type and Prx1 knockout mice were treated with 50 µg/ml 4‑nitroquinoline‑1‑oxide (4NQO) or 4NQO + H2O2 for 16 weeks to establish mouse models with tongue precancerous lesions. Apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay. The expression of Prx1, apoptosis signal‑regulating kinase 1 (ASK1), phosphor‑ASK1, p38 and phosphor‑p38 was analyzed using immunohistochemical staining, and their mRNA expression levels were evaluated by reverse transcription quantitative polymerase chain reaction. The present results demonstrated that 4NQO or 4NQO + H2O2 induced the development of tongue precancerous lesions in Prx1 knockout and wild‑type mice. Prx1 was overexpressed in tongue precancerous lesions compared with normal tongue mucosa. There was a significant decrease in the degree of moderate or severe epithelial dysplasia, and mild epithelial dysplasia was clearly elevated, in Prx1 knockout mice treated with 4NQO + H2O2 compared with wild‑type mice treated with 4NQO + H2O2. Prx1 suppressed apoptosis and upregulated phosphor‑ASK1 and phosphor‑p38 expression in tongue precancerous lesions. The present results suggest that Prx1 suppresses oxidative stress‑induced apoptosis via the ASK1/p38 signalling pathway in mouse tongue precancerous lesions. In conclusion, Prx1 and H2O2 have a coordination role in promoting the progression of tongue precancerous mucosa lesions. The present findings provide novel insight into Prx1 function and the mechanisms of Prx1 in OLK pathogenesis.

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