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Externalization of phosphatidylserine via multidrug resistance 1 (MDR1)/P-glycoprotein in oxalate-treated renal epithelial cells: implications for calcium oxalate urolithiasis

  • Urology - Original Paper
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Abstract

Objectives

We investigated the possible involvement of multidrug resistance protein 1 P-glycoprotein (MDR1 P-gp) in the oxalate-induced redistribution of phosphatidylserine in renal epithelial cell membranes.

Methods

Real-time PCR and western blotting were used to examine MDR1 expression in Madin–Darby canine kidney cells at the mRNA and protein levels, respectively, whereas surface-expressed phosphatidylserine was detected by the annexin V-binding assay.

Results

Oxalate treatment resulted in increased synthesis of MDR1, which resulted in phosphatidylserine (PS) externalization in the renal epithelial cell membrane. Treatment with the MDR1 inhibitor PSC833 significantly attenuated phosphatidylserine externalization. Transfection of the human MDR1 gene into renal epithelial cells significantly increased PS externalization.

Conclusions

To our knowledge, this study is the first to show that oxalate increases the synthesis of MDR1 P-gp, which plays a key role in hyperoxaluria-promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant Number 81370803).

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Authors and Affiliations

  1. Department of Urology Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China

    Yu-Hang Li, Shi-Liang Yu, Xiu-Guo Gan & Rui-Hua An

  2. Department of Central Laboratory, First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China

    Shang-Ha Pan

  3. Department of Central Laboratory of Blood Cancer, First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China

    Yue-Qiu Teng

Authors
  1. Yu-Hang Li
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  2. Shi-Liang Yu
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Corresponding author

Correspondence to Rui-Hua An.

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Conflict of interest

Yu-Hang Li declares that he has no conflict of interest. Shi-Liang Yu declares that he has no conflict of interest. Xiu-Guo Gan declares that he has no conflict of interest. Shang-Ha Pan declares that he has no conflict of interest. Yue-Qiu Teng declares that she has no conflict of interest. Rui-Hua An declares that he has no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Li, YH., Yu, SL., Gan, XG. et al. Externalization of phosphatidylserine via multidrug resistance 1 (MDR1)/P-glycoprotein in oxalate-treated renal epithelial cells: implications for calcium oxalate urolithiasis. Int Urol Nephrol 48, 175–181 (2016). https://doi.org/10.1007/s11255-015-1155-1

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  • DOI: https://doi.org/10.1007/s11255-015-1155-1

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