Proteome profiling to identify peroxiredoxin 1 interacting protein partners in nicotine-associated oral leukoplakia
| Autor: | Jing Yang, Xiaofei Tang, Lingyu Li, Lihua Ge, Min Wang, Ni Shi, Tong Chen, Moci Qi, Min Zhang, Hui Chen, Yunping Lu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
rho GTP-Binding Proteins
0301 basic medicine Nicotine Proteome Peroxiredoxin 1 Biology MAP Kinase Kinase Kinase 5 DNA-binding protein Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Western blot GTP-Binding Proteins Tandem Mass Spectrometry medicine Animals Humans ASK1 General Dentistry Homeodomain Proteins medicine.diagnostic_test Kinase Smoking Nuclear Proteins Peroxiredoxins 030206 dentistry Cell Biology General Medicine 030104 developmental biology Otorhinolaryngology Carcinoma Squamous Cell Cancer research Mouth Neoplasms Leukoplakia Oral Thioredoxin Chromatography Liquid medicine.drug |
| Zdroj: | Archives of Oral Biology. 108:104537 |
| ISSN: | 0003-9969 |
| DOI: | 10.1016/j.archoralbio.2019.104537 |
| Popis: | Objective Tobacco smoking is one of the main risk factors for oral squamous cell carcinoma (OSCC) and can induce generation of reactive oxygen species (ROS). In our previous studies, we demonstrated that nicotine, the major ingredient in tobacco, can upregulate an important antioxidant enzyme Peroxiredoxin 1 (Prx1), in oral leukoplakia (OLK), an oral precancerous lesion. The underlying regulatory mechanisms, however, remain unclear. This study aims to identify regulatory mechanisms of nicotine and identify Prx1 interacting proteins in nicotine-associated OLK. Design Liquid chromatography-tandem mass spectrometry (LC–MS/MS) combined with bioinformatics analysis was conducted to profile Prx1 binding proteins in human dysplastic oral keratinocyte (DOK) cells. Candidate interaction proteins were further verified using Co-immunoprecipitation (Co-IP), Western blot or Duolink assay in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK in mice and human OLK tissues. Results We identified Thioredoxin (Trx), Nucleolar GTP-binding protein 1 (GTPBP4), GTP-binding protein Di-Ras2 (DIRAS2) and apoptosis signal-regulating kinase 1 (ASK1) as key Prx1 interacting proteins regulated by nicotine. Our data showed that nicotine upregulated Trx, GTPBP4, DIRAS2, and downregulated ASK1 in 4NQO-induced OLK in mice, at least in part dependent on Prx1. The modulations of Trx, GTPBP4, DIRAS2 and ASK1 by nicotine were also found in OLK smokers compared to OLK non-smokers. The in-situ interaction of Trx, GTPBP4, DIRAS2 and ASK1 with Prx1 were validated in human OLK tissues. Conclusion Nicotine may promote OLK development via regulating Prx1 binding proteins Trx, GTPBP4, DIRAS2 and ASK1. The results of this study will help to develop therapeutic approaches for OLK in humans targeting Prx1 interacting protein network. |
| Databáze: | OpenAIRE |
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