Peroxiredoxin 1 suppresses apoptosis via regulation of the apoptosis signal-regulating kinase 1 signaling pathway in human oral leukoplakia

Zhang,Min; Niu,Wenwen; Zhang,Jianfei; Ge,Lihua; Yang,Jing; Sun,Zheng; Tang,Xiaofei

doi:10.3892/ol.2015.3424

Peroxiredoxin 1 suppresses apoptosis via regulation of the apoptosis signal-regulating kinase 1 signaling pathway in human oral leukoplakia

Authors:
- Min Zhang
- Wenwen Niu
- Jianfei Zhang
- Lihua Ge
- Jing Yang
- Zheng Sun
- Xiaofei Tang
View Affiliations

Affiliations: Beijing Institute of Dental Research, Beijing Key Laboratory, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing 100050, P.R. China
Published online on: June 25, 2015 https://doi.org/10.3892/ol.2015.3424
Pages: 1841-1847

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Messadi DV: Diagnostic aids for detection of oral precancerous conditions. Int J Oral Sci. 5:59–65. 2013. View Article : Google Scholar : PubMed/NCBI
2	van der Waal I: Oral potentially malignant disorders: Is malignant transformation predictable and preventable? Med Oral Patol Oral Cir Bucal. 19:e386–e390. 2014. View Article : Google Scholar : PubMed/NCBI
3	Neville BW and Day TA: Oral cancer and precancerous lesions. CA Cancer J Clin. 52:195–215. 2002. View Article : Google Scholar : PubMed/NCBI
4	Nayyar AS and Khan M: In search of malignant transformation: A pilot study. J Cancer Res Ther. 8:277–281. 2012. View Article : Google Scholar : PubMed/NCBI
5	Metgud R and Bajaj S: Evaluation of salivary and serum lipid peroxidation, and glutathione in oral leukoplakia and oral squamous cell carcinoma. J Oral Sci. 56:135–142. 2014. View Article : Google Scholar : PubMed/NCBI
6	Yanagawa T, Iwasa S, Ishii T, Tabuchi K, Yusa H, Onizawa K, Omura K, Harada H, Suzuki H and Yoshida H: Peroxiredoxin I expression in oral cancer: A potential new tumor marker. Cancer Lett. 156:27–35. 2000. View Article : Google Scholar : PubMed/NCBI
7	Cha MK, Suh KH and Kim IH: Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma. J Exp Clin Cancer Res. 28:932009. View Article : Google Scholar : PubMed/NCBI
8	Zhao YH, Zhang M, Yan F, Casto BC and Tang XF: Nicotine-induced upregulation of antioxidant protein Prx 1 in oral squamous cell carcinoma. Chin Sci Bull. 58:1912–1918. 2013. View Article : Google Scholar
9	Turner-Ivey B, Manevich Y, Schulte J, Kistner-Griffin E, Jezierska-Drutel A, Liu Y and Neumann CA: Role for Prdx1 as a specific sensor in redox-regulated senescence in breast cancer. Oncogene. 32:5302–5314. 2013. View Article : Google Scholar : PubMed/NCBI
10	Kim YJ, Lee WS, Ip C, Chae HZ, Park EM and Park YM: Prx1 suppresses radiation-induced c-Jun NH2-terminal kinase signaling in lung cancer cells through interaction with the glutathione S-transferase Pi/c-Jun NH2-terminal kinase complex. Cancer Res. 66:7136–7142. 2006. View Article : Google Scholar : PubMed/NCBI
11	Turjanski AG, Vaqué JP and Gutkind JS: MAP kinases and the control of nuclear events. Oncogene. 26:3240–3253. 2007. View Article : Google Scholar : PubMed/NCBI
12	Kim SY, Kim TJ and Lee KY: A novel function of peroxiredoxin 1 (Prx-1) in apoptosis signal-regulating kinase 1 (ASK1)-mediated signaling pathway. FEBS Lett. 582:1913–1918. 2008. View Article : Google Scholar : PubMed/NCBI
13	Wu Z, Sheng H, Chen Y, Tang J, Liu Y, Chen Q, Lu L and Jin W: Copy number variation of the Lipoprotein(a) (LPA) gene is associated with coronary artery disease in a southern Han Chinese population. Int J Clin Exp Med. 7:3669–3677. 2014.PubMed/NCBI
14	Lowry OH, Rosebrough NJ, Farr AL and Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem. 193:265–275. 1951.PubMed/NCBI
15	Memon AA, Chang JW, Oh BR and Yoo YJ: Identification of differentially expressed proteins during human urinary bladder cancer progression. Cancer Detect Prev. 29:249–255. 2005. View Article : Google Scholar : PubMed/NCBI
16	Xie Q, Zhou Y, Lan G, Yang L, Zheng W, Liang Y and Chen T: Sensitization of cancer cells to radiation by selenadiazole derivatives by regulation of ROS-mediated DNA damage and ERK and AKT pathways. Biochem Biophys Res Commun. 449:88–93. 2014. View Article : Google Scholar : PubMed/NCBI
17	Ge LH, Hou M, Yang J, Chen T and Tang XF: Prx1 overexpression in human OLK. Beijing J Stomatology. 20:135–137. 2012.
18	Chatterjee S, Feinstein SI, Dodia C, Sorokina E, Lien YC, Nguyen S, Debolt K, Speicher D and Fisher AB: Peroxiredoxin 6 phosphorylation and subsequent phospholipase A2 activity are required for agonist-mediated activation of NADPH oxidase in mouse pulmonary microvascular endothelium and alveolar macrophages. J Biol Chem. 286:11696–11706. 2011. View Article : Google Scholar : PubMed/NCBI
19	Tang XF, Zhang XY and Zhang M: The differences expression of oxidative stress-related genes in oral cancer and precancerous cells. Beijing J Stomatology. 16:308–311. 2008.
20	Zhang JF, Tang XF, Ge LH, Yang J, Niu WW, Zhang M and Chen T: Role of apoptosis signal-regulating kinase 1 in the cell apoptosis in oral leukoplakia. Beijing J Stomatology. 22:65–69. 2014.
21	Nakagawa H, Hirata Y, Takeda K, Hayakawa Y, Sato T, Kinoshita H, Sakamoto K, Nakata W, Hikiba Y, Omata M, et al: Apoptosis signal-regulating kinase 1 inhibits hepatocarcinogenesis by controlling the tumor-suppressing function of stress-activated mitogen-activated protein kinase. Hepatology. 54:185–195. 2011. View Article : Google Scholar : PubMed/NCBI
22	Hayakawa Y, Hirata Y, Nakagawa H, Sakamoto K, Hikiba Y, Kinoshita H, Nakata W, Takahashi R, Tateishi K, Tada M, et al: Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer. Proc Natl Acad Sci USA. 108:780–785. 2011. View Article : Google Scholar : PubMed/NCBI
23	Koul HK, Pal M and Koul S: Role of p38 MAP kinase signal transduction in solid tumors. Genes Cancer. 4:342–359. 2013. View Article : Google Scholar : PubMed/NCBI
24	Che JP, Li W, Yan Y, Liu M, Wang GC, Li QY, Yang B, Yao XD and Zheng JH: Expression and clinical significance of the nin one binding protein and p38 MAPK in prostate carcinoma. Int J Clin Exp Pathol. 6:2300–2311. 2013.PubMed/NCBI
25	Takeda K, Matsuzawa A, Nishitoh H and Ichijo H: Roles of MAPKKK ASK1 in stress-induced cell death. Cell Struct Funct. 28:23–29. 2003. View Article : Google Scholar : PubMed/NCBI
26	Soqa M, Matsuzawa A and Ichijo H: Oxidative stress-induced diseases via the ASK1 signaling pathway. Int J Cell Biol. 2012:4395872012.PubMed/NCBI
27	Du ZX, Yan Y, Zhang HY, Liu BQ, Gao YY, Niu XF, Guan Y, Meng X and Wang HQ: Suppression of MG132-mediated cell death by peroxiredoxin 1 through influence on ASK1 activation in human thyroid cancer cells. Endocr Relat Cancer. 17:553–560. 2010. View Article : Google Scholar : PubMed/NCBI
28	Lee YM, Park SH, Shin DI, Hwang JY, Park B, Park YJ, Lee TH, Chae HZ, Jin BK, Oh TH, et al: Oxidative modification of peroxiredoxin is associated with drug-induced apoptotic signaling in experimental models of Parkinson disease. J Biol Chem. 283:9986–9998. 2008. View Article : Google Scholar : PubMed/NCBI
29	Jarvis RM, Hughes SM and Ledgerwood EC: Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells. Free Radic Biol Med. 53:1522–1530. 2012. View Article : Google Scholar : PubMed/NCBI