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Augmenter of liver regeneration plays a protective role against hydrogen peroxide-induced oxidative stress in renal proximal tubule cells

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Abstract

Oxidative stress plays an important role in cellular destruction. Augmenter of liver regeneration (ALR) is an anti-apoptotic factor that is expressed in all mammalian cells and functions as an anti-oxidant by stimulating the expression of a secretory isoform of clusterin and inhibiting reactive oxygen species (ROS) generation. Previous work from our group showed that ALR expression is upregulated in acute kidney injury (AKI) rats, and recombinant human ALR reduces tubular injury. In the present study, we used small interfering RNA (siRNA) silencing of ALR to examine its role in H2O2 induced mitochondrial injury and apoptosis. Knockdown of ALR increased ROS levels, reduced mitochondrial membrane potential, and increased the release of mitochondrial proteins and the rate of apoptosis in response to H2O2. In addition, the ratio of Bax/Bcl-2 was increased in siRNA/ALR groups treated with H2O2. These data confirm the protective role of ALR against oxidative stress-induced mitochondrial injury and suggest a potential mechanism underlying the protective role of ALR in AKI.

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Abbreviations

ALR:

Augmenter of liver regeneration

AKI:

Acute kidney injury

ROS:

Reactive oxygen species

MMP:

Mitochondrial membrane potential

DCFH-DA:

2-,7-Dichlorofluorescin diacetate

DAPI:

4′,6-Diamidino-2-phenylindole

H2O2 :

Hydrogen peroxide

MTS:

3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt

COX IV:

Cytochrome c oxidase IV

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Acknowledgments

This work was supported by a Grant from the National Natural Science Foundation of China (39071364) and clinical medicine research special funds of the Chinese medical association (14050370574), and Grants from medical scientific research Projects of Chongqing health and family planning commission (20142031).

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Authors and Affiliations

  1. Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

    Ning Xia, Ru-yu Yan, Xiao-hui Liao & Ling Zhang

  2. Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

    Qi Liu, Hang Sun & Hui Guo

Authors
  1. Ning Xia
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  2. Ru-yu Yan
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  3. Qi Liu
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  4. Xiao-hui Liao
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  5. Hang Sun
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  6. Hui Guo
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  7. Ling Zhang
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Correspondence to Ling Zhang.

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Xia, N., Yan, Ry., Liu, Q. et al. Augmenter of liver regeneration plays a protective role against hydrogen peroxide-induced oxidative stress in renal proximal tubule cells. Apoptosis 20, 423–432 (2015). https://doi.org/10.1007/s10495-015-1096-2

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