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Blocking P2X7 receptor ameliorates oxidized LDL-mediated podocyte apoptosis

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Abstract

The purpose of our research is to elucidate whether oxLDL activates P2X7R in cultured human podocytes and if the activation of P2X7R leads to podocyte apoptosis. Additionally, we explore the underlying mechanism involved in podocyte apoptosis. Immortalized human podocytes were incubated with oxLDL (80 µg/ml), P2X7R antagonist A438079 (10 µM), or the compound of A438079 and oxLDL for 48 h, respectively. Cellular apoptosis and ROS were evaluated using flow cytometer. P2X7R, Bax, and Caspase-3 protein expression were detected by western blot and immunofluorescence analysis.The expression of P2X7R, ROS, Bax, and Caspase-3 in human podocytes incubated with oxLDL was significantly up-regulated and was found to have higher intracellular lipid accumulation and podocyte apoptosis compared with the NC group. However, co-administration with A438079, ROS, Bax, and Caspase-3 expression both significantly down-regulate as well as lower lipid accumulation and cellular apoptosis in the oxLDL-induced podocyte group. We revealed that P2X7R is involved in the regulation of oxLDL-treated podocytes. Additionally, we found that the anti-apoptotic effect of A438079 is correlated with ROS, Bax, and Caspase-3 expression down-regulated.

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Acknowledgements

This work is funded by the Natural Science Foundation of Shandong Province (ZR2015HM009) and Shandong Key R&D Program (2017 GSF218005).

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Authors and Affiliations

  1. Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jing Wu Road, Jinan, 250021, People’s Republic of China

    Yanji Zhu, Qian Li, Yuan Chen, Caihui Zhang & Shuzhen Sun

  2. Department of Pediatrics, People’s Hospital of Rizhao, Rizhao, 276800, People’s Republic of China

    Yanji Zhu & Wenlong Xun

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  1. Yanji Zhu
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  2. Qian Li
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  3. Wenlong Xun
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  4. Yuan Chen
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  5. Caihui Zhang
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Correspondence to Shuzhen Sun.

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Zhu, Y., Li, Q., Xun, W. et al. Blocking P2X7 receptor ameliorates oxidized LDL-mediated podocyte apoptosis. Mol Biol Rep 46, 3809–3816 (2019). https://doi.org/10.1007/s11033-019-04823-6

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  • DOI: https://doi.org/10.1007/s11033-019-04823-6

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