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

Li,Zhuohang; Sheng,Yiyu; Liu,Cheng; Li,Kuiqing; Huang,Xin; Huang,Jian; Xu,Kewei

doi:10.3892/mmr.2016.5083

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

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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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