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Article

Nox4 has a crucial role in uric acid‑induced oxidative stress and apoptosis in renal tubular cells

  • Authors:
    • Zhuohang Li
    • Yiyu Sheng
    • Cheng Liu
    • Kuiqing Li
    • Xin Huang
    • Jian Huang
    • Kewei Xu
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China
  • Pages: 4343-4348
    |
    Published online on: April 4, 2016
       https://doi.org/10.3892/mmr.2016.5083
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Abstract

The purpose of the present study was to evaluate the effects of uric acid in promoting tubular cell apoptosis and verify the role of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4)‑induced oxidative stress in this process. HK‑2 cells were used as a human proximal tubular cell model and co‑cultured with various concentrations of uric acid with or without pre‑treatment with the Nox4 inhibitor diphenylene iodonium (DPI). The apoptotic rate and the amount of reactive oxygen species (ROS) were examined by flow cytometry. Furthermore, levels of Nox4, phosphorylated (p)‑P38, p‑extracellular signal‑regulated kinase (ERK), B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑extra large (Bax) were detected by western blot analysis. The results showed that treatment with uric acid decreased HK‑2 cell viability and promoted apoptosis in a dose‑dependent manner. This was paralleled with an upregulation of Nox4 as well as ROS overproduction, which activated the phosphorylation of P38/ERK and caused an imbalance of Bax/Bcl‑2 in HK‑2 cells. Of note, inhibition of Nox4 with DPI prevented uric acid‑induced cell injury by suppressing ROS generation and P38/ERK activation. In conclusion, it was demonstrated that elevated uric acid promoted ROS‑induced tubular cell apoptosis by upregulating Nox4 expression. The present study therefore provided possible mechanisms and a potential therapeutic target of uric acid‑induced chronic kidney disease.
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1 

Obermayr RP, Temml C, Gutjahr G, Knechtelsdorfer M, Oberbauer R and Klauser-Braun R: Elevated uric acid increases the risk for kidney disease. J Am Soc Nephrol. 19:2407–2413. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Johnson RJ, Nakagawa T, Jalal D, Sánchez-Lozada LG, Kang DH and Ritz E: Uric acid and chronic kidney disease: Which is chasing which? Nephrol Dial Transplant. 28:2221–2228. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Jin M, Yang F, Yang I, Yin Y, Luo JJ, Wang H and Yang XF: Uric acid, hyperuricemia and vascular diseases. Front Biosci (Landmark Ed). 17:656–669. 2012. View Article : Google Scholar

4 

Convento MS, Pessoa E, Dalboni MA, Borges FT and Schor N: Pro-inflammatory and oxidative effects of noncrystalline uric acid in human mesangial cells: Contribution to hyperuricemic glomerular damage. Urol Res. 39:21–27. 2011. View Article : Google Scholar

5 

Corry DB, Eslami P, Yamamoto K, Nyby MD, Makino H and Tuck ML: Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens. 26:269–275. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Zhang JX, Zhang YP, Wu QN and Chen B: Uric acid induces oxidative stress via an activation of the renin-angiotensin system in 3T3-L1 adipocytes. Endocrine. 48:135–142. 2015. View Article : Google Scholar

7 

Ago T, Kuroda J, Pain J, Fu C, Li H and Sadoshima J: Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res. 106:1253–1264. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Sedeek M, Nasrallah R, Touyz RM and Hébert RL: NADPH oxidases, reactive oxygen species, and the kidney: Friend and foe. J Am Soc Nephrol. 24:1512–1518. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Brown DI and Griendling KK: Regulation of signal transduction by reactive oxygen species in the cardiovascular system. Circ Res. 116:531–549. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Havasi A and Borkan SC: Apoptosis and acute kidney injury. Kidney Int. 80:29–40. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Sharma K: Obesity, oxidative stress, and fibrosis in chronic kidney disease. Kidney Int Suppl. 4:113–117. 2014. View Article : Google Scholar

12 

Park J, Min JS, Kim B, Chae UB, Yun JW, Choi MS, Kong IK, Chang KT and Lee DS: Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-kB pathways. Neurosci Lett. 584:191–196. 2015. View Article : Google Scholar

13 

Zhao ZY, Luan P, Huang SX, Xiao SH, Zhao J, Zhang B, Gu BB, Pi RB and Liu J: Edaravone protects HT22 neurons from H2O2-induced apoptosis by inhibiting the MAPK signaling pathway. CNS Neurosci Ther. 19:163–169. 2013. View Article : Google Scholar

14 

Changchien JJ, Chen YJ, Huang CH, Cheng TL, Lin SR and Chang LS: Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression. Toxicol Appl Pharmacol. 284:33–41. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Liu W, Ning R, Chen RN, Huang XF, Dai QS, Hu JH, Wang YW, Wu LL, Xiong J, Hu G, et al: Aspafilioside B induces G2/M cell cycle arrest and apoptosis by up-regulating H-Ras and N-Ras via ERK and p38 MAPK signaling pathways in human hepatoma HepG2 cells. Mol Carcinog. Feb 14–2015.Epub ahead of print.

16 

Shi M, He X, Wei W, Wang J, Zhang T and Shen X: Tenascin-C induces resistance to apoptosis in pancreatic cancer cell through activation of ERK/NF-kB pathway. Apoptosis. 20:843–857. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Liu Y, Zhang S, Su D, Liu J, Cheng Y, Zou L, Li W and Jiang Y: Inhibiting (pro)renin receptor-mediated p38 MAPK signaling decreases hypoxia/reoxygenation-induced apoptosis in H9c2 cells. Mol Cell Biochem. 403:267–276. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Boban M, Kocic G, Radenkovic S, Pavlovic R, Cvetkovic T, Deljanin-Ilic M, Ilic S, Bobana MD, Djindjic B, Stojanovic D, et al: Circulating purine compounds, uric acid, and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease. Ren Fail. 36:613–618. 2014. View Article : Google Scholar : PubMed/NCBI

19 

He T, Guan X, Wang S, Xiao T, Yang K, Xu X, Wang J and Zhao J: Resveratrol prevents high glucose-induced epithelial-mesenchymal transition in renal tubular epithelial cells by inhibiting NADPH oxidase/ROS/ERK pathway. Mol Cell Endocrinol. 402:13–20. 2015. View Article : Google Scholar

20 

Zhang Y, Yamamoto T, Hisatome I, Li Y, Cheng W, Sun N, Cai B, Huang T, Zhu Y, Li Z, et al: Uric acid induces oxidative stress and growth inhibition by activating adenosine monophosphate-activated protein kinase and extracellular signal-regulated kinase signal pathways in pancreatic β cells. Mol Cell Endocrinol. 375:89–96. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Mouche S, Mkaddem SB, Wang W, Katic M, Tseng YH, Carnesecchi S, Steger K, Foti M, Meier CA, Muzzin P, et al: Reduced expression of the NADPH oxidase NOX4 is a hallmark of adipocyte differentiation. Biochim Biophys Acta. 1773:1015–1027. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Kawahara T, Quinn MT and Lambeth JD: Molecular evolution of the reactive oxygen-generating NADPH oxidase (Nox/Duox) family of enzymes. BMC Evol Biol. 7:1092007. View Article : Google Scholar : PubMed/NCBI

23 

Sedeek M, Callera G, Montezano A, Gutsol A, Heitz F, Szyndralewiez C, Page P, Kennedy CR, Burns KD, Touyz RM and Hébert RL: Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: Implications in type 2 diabetic nephropathy. Am J Physiol Renal Physiol. 299:F1348–F1358. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Kim SM, Kim YG, Jeong KH, et al: Angiotensin II-induced mitochondrial Nox4 is a major endogenous source of oxidative stress in kidney tubular cells. PLoS One. 7:e397392012. View Article : Google Scholar : PubMed/NCBI

25 

Oh SW, Lee ES, Kim S, Na KY, Chae DW, Kim S and Chin HJ: Bilirubin attenuates the renal tubular injury by inhibition of oxidative stress and apoptosis. BMC Nephrol. 14:1052013. View Article : Google Scholar : PubMed/NCBI

26 

Qi W, Niu J, Qin Q, Qiao Z and Gu Y: Glycated albumin triggers fibrosis and apoptosis via an NADPH oxidase/Nox4-MAPK pathway-dependent mechanism in renal proximal tubular cells. Mol Cell Endocrinol. 405:74–83. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Gao X, Wu J, Qian Y, et al: Oxidized high-density lipoprotein impairs the function of human renal proximal tubule epithelial cells through CD36. Int J Mol Med. 34:564–572. 2014.PubMed/NCBI

28 

Jaiman S, Sharma AK, Singh K and Khanna D: Signalling mechanisms involved in renal pathological changes during cisplatin-induced nephropathy. Eur J Clin Pharmacol. 69:1863–1874. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Quan H, Peng X, Liu S, Bo F, Yang L, Huang Z, Li H, Chen X and Di W: Differentially expressed protein profile of renal tubule cell stimulated by elevated uric acid using SILAC coupled to LC-MS. Cell Physiol Biochem. 27:91–98. 2011.PubMed/NCBI

30 

Verzola D, Ratto E, Villaggio B, Parodi EL, Pontremoli R, Garibotto G and Viazzi F: Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4. PLoS One. 9:e1152102014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li Z, Sheng Y, Liu C, Li K, Huang X, Huang J and Xu K: Nox4 has a crucial role in uric acid‑induced oxidative stress and apoptosis in renal tubular cells. Mol Med Rep 13: 4343-4348, 2016.
APA
Li, Z., Sheng, Y., Liu, C., Li, K., Huang, X., Huang, J., & Xu, K. (2016). Nox4 has a crucial role in uric acid‑induced oxidative stress and apoptosis in renal tubular cells. Molecular Medicine Reports, 13, 4343-4348. https://doi.org/10.3892/mmr.2016.5083
MLA
Li, Z., Sheng, Y., Liu, C., Li, K., Huang, X., Huang, J., Xu, K."Nox4 has a crucial role in uric acid‑induced oxidative stress and apoptosis in renal tubular cells". Molecular Medicine Reports 13.5 (2016): 4343-4348.
Chicago
Li, Z., Sheng, Y., Liu, C., Li, K., Huang, X., Huang, J., Xu, K."Nox4 has a crucial role in uric acid‑induced oxidative stress and apoptosis in renal tubular cells". Molecular Medicine Reports 13, no. 5 (2016): 4343-4348. https://doi.org/10.3892/mmr.2016.5083
Copy and paste a formatted citation
x
Spandidos Publications style
Li Z, Sheng Y, Liu C, Li K, Huang X, Huang J and Xu K: Nox4 has a crucial role in uric acid‑induced oxidative stress and apoptosis in renal tubular cells. Mol Med Rep 13: 4343-4348, 2016.
APA
Li, Z., Sheng, Y., Liu, C., Li, K., Huang, X., Huang, J., & Xu, K. (2016). Nox4 has a crucial role in uric acid‑induced oxidative stress and apoptosis in renal tubular cells. Molecular Medicine Reports, 13, 4343-4348. https://doi.org/10.3892/mmr.2016.5083
MLA
Li, Z., Sheng, Y., Liu, C., Li, K., Huang, X., Huang, J., Xu, K."Nox4 has a crucial role in uric acid‑induced oxidative stress and apoptosis in renal tubular cells". Molecular Medicine Reports 13.5 (2016): 4343-4348.
Chicago
Li, Z., Sheng, Y., Liu, C., Li, K., Huang, X., Huang, J., Xu, K."Nox4 has a crucial role in uric acid‑induced oxidative stress and apoptosis in renal tubular cells". Molecular Medicine Reports 13, no. 5 (2016): 4343-4348. https://doi.org/10.3892/mmr.2016.5083
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