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Apoptosis

, Volume 23, Issue 11–12, pp 695–706 | Cite as

Augmenter of liver regeneration promotes mitochondrial biogenesis in renal ischemia–reperfusion injury

  • Li-li Huang
  • Rui-ting Long
  • Gui-ping Jiang
  • Xiao Jiang
  • Hang Sun
  • Hui Guo
  • Xiao-hui LiaoEmail author
Article

Abstract

Mitochondria are the center of energy metabolism in the cell and the preferential target of various toxicants and ischemic injury. Renal ischemia–reperfusion (I/R) injury triggers proximal tubule injury and the mitochondria are believed to be the primary subcellular target of I/R injury. The promotion of mitochondrial biogenesis (MB) is critical for the prevention I/R injury. The results of our previous study showed that augmenter of liver regeneration (ALR) has anti-apoptotic and anti-oxidant functions. However, the modulatory mechanism of ALR remains unclear and warrants further investigation. To gain further insight into the role of ALR in MB, human kidney (HK)-2 cells were treated with lentiviruses carrying ALR short interfering RNA (siRNA) and a model of hypoxia reoxygenation (H/R) injury in vitro was created. We observed that knockdown of ALR promoted apoptosis of renal tubular cells and aggravated mitochondrial injury, as evidenced by the decrease in the mitochondrial respiratory proteins adenosine triphosphate (ATP) synthase subunit β, cytochrome c oxidase subunit 1, and nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) beta subcomplex 8. Meanwhile, the production of reactive oxygen species was increased and ATP levels were decreased significantly in HK-2 cells, as compared with the siRNA/control group (p < 0.05). In addition, the mitochondrial DNA copy number and membrane potential were markedly decreased. Furthermore, critical transcriptional regulators of MB (i.e., peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, mitochondrial transcription factor A, sirtuin-1, and nuclear respiratory factor-1) were depleted in the siRNA/ALR group. Taken together, these findings unveil essential roles of ALR in the inhibition of renal tubular cell apoptosis and attenuation of mitochondrial dysfunction by promoting MB in AKI.

Keywords

Augmenter of liver regeneration Mitochondrial biogenesis Ischemia–reperfusion injury Reactive oxygen species 

Notes

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81873604, 30971364), the Natural Science Foundation Project of CQ CSTC (cstc2015jcyjA10069), the Medical Scientific Research Projects of the Chongqing Health and Family Planning Commission (20142031), and the Fund for Fostering Talent in Scientific Research of Chongqing Medical University (201404).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest or financial interests to declare.

References

  1. 1.
    Chalkias A, Xanthos T (2012) Acute kidney injury. The Lancet 380(9857):1904.  https://doi.org/10.1016/s0140-6736(12)62104-7 CrossRefGoogle Scholar
  2. 2.
    Waikar SS, Liu KD, Chertow GM (2008) Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol 3(3):844–861.  https://doi.org/10.2215/CJN.05191107 CrossRefPubMedGoogle Scholar
  3. 3.
    Lo LJ, Go AS, Chertow GM, McCulloch CE, Fan D, Ordonez JD, Hsu CY (2009) Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease. Kidney Int 76(8):893–899.  https://doi.org/10.1038/ki.2009.289 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Verma SK, Molitoris BA (2015) Renal endothelial injury and microvascular dysfunction in acute kidney injury. Semin Nephrol 35(1):96–107.  https://doi.org/10.1016/j.semnephrol.2015.01.010 CrossRefPubMedGoogle Scholar
  5. 5.
    Kim J, Jung KJ, Park KM (2010) Reactive oxygen species differently regulate renal tubular epithelial and interstitial cell proliferation after ischemia and reperfusion injury. Am J Physiol Renal Physiol 298(5):F1118–F1129.  https://doi.org/10.1152/ajprenal.00701.2009 CrossRefPubMedGoogle Scholar
  6. 6.
    Wang Z, Ying Z, Bosy-Westphal A, Zhang J, Schautz B, Later W, Heymsfield SB, Muller MJ (2010) Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure. Am J Clin Nutr 92(6):1369–1377.  https://doi.org/10.3945/ajcn.2010.29885 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    O’Connor PM (2006) Renal oxygen delivery: matching delivery to metabolic demand. Clin Exp Pharmacol Physiol 33(10):961–967.  https://doi.org/10.1111/j.1440-1681.2006.04475.x CrossRefPubMedGoogle Scholar
  8. 8.
    Bhargava P, Schnellmann RG (2017) Mitochondrial energetics in the kidney. Nat Rev Nephrol 13(10):629–646.  https://doi.org/10.1038/nrneph.2017.107 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Plotnikov EY, Kazachenko AV, Vyssokikh MY, Vasileva AK, Tcvirkun DV, Isaev NK, Kirpatovsky VI, Zorov DB (2007) The role of mitochondria in oxidative and nitrosative stress during ischemia/reperfusion in the rat kidney. Kidney Int 72(12):1493–1502.  https://doi.org/10.1038/sj.ki.5002568 CrossRefPubMedGoogle Scholar
  10. 10.
    Stallons LJ, Whitaker RM, Schnellmann RG (2014) Suppressed mitochondrial biogenesis in folic acid-induced acute kidney injury and early fibrosis. Toxicol Lett 224(3):326–332.  https://doi.org/10.1016/j.toxlet.2013.11.014 CrossRefPubMedGoogle Scholar
  11. 11.
    Funk JA, Schnellmann RG (2012) Persistent disruption of mitochondrial homeostasis after acute kidney injury. Am J Physiol Renal Physiol 302(7):F853–F864.  https://doi.org/10.1152/ajprenal.00035.2011 CrossRefPubMedGoogle Scholar
  12. 12.
    Peterson YK, Cameron RB, Wills LP, Trager RE, Lindsey CC, Beeson CC, Schnellmann RG (2013) beta2-Adrenoceptor agonists in the regulation of mitochondrial biogenesis. Bioorg Med Chem Lett 23(19):5376–5381.  https://doi.org/10.1016/j.bmcl.2013.07.052 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Gupta P, Venugopal SK (2018) Augmenter of liver regeneration: a key protein in liver regeneration and pathophysiology. Hepatol Res 48(8):587–596.  https://doi.org/10.1111/hepr.13077 CrossRefPubMedGoogle Scholar
  14. 14.
    Balogh T, Szarka A (2015) [ALR, the multifunctional protein]. Orv Hetil 156(13):503–509.  https://doi.org/10.1556/OH.2015.30119 CrossRefPubMedGoogle Scholar
  15. 15.
    Ozer HK, Dlouhy AC, Thornton JD, Hu J, Liu Y, Barycki JJ, Balk J, Outten CE (2015) Cytosolic Fe-S cluster protein maturation and iron regulation are independent of the mitochondrial Erv1/Mia40 import system. J Biol Chem 290(46):27829–27840.  https://doi.org/10.1074/jbc.M115.682179 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mordas A, Tokatlidis K (2015) The MIA pathway: a key regulator of mitochondrial oxidative protein folding and biogenesis. Acc Chem Res 48(8):2191–2199.  https://doi.org/10.1021/acs.accounts.5b00150 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Weng J, Li W, Jia X, An W (2017) Alleviation of ischemia–reperfusion injury in liver steatosis by augmenter of liver regeneration is attributed to antioxidation and preservation of mitochondria. Transplantation 101(10):2340–2348.  https://doi.org/10.1097/TP.0000000000001874 CrossRefGoogle Scholar
  18. 18.
    Gandhi CR, Chaillet JR, Nalesnik MA, Kumar S, Dangi A, Demetris AJ, Ferrell R, Wu T, Divanovic S, Stankeiwicz T, Shaffer B, Stolz DB, Harvey SA, Wang J, Starzl TE (2015) Liver-specific deletion of augmenter of liver regeneration accelerates development of steatohepatitis and hepatocellular carcinoma in mice. Gastroenterology 148(2):379–391 e374.  https://doi.org/10.1053/j.gastro.2014.10.008 CrossRefPubMedGoogle Scholar
  19. 19.
    Xia N, Yan RY, Liu Q, Liao XH, Sun H, Guo H, Zhang L (2015) Augmenter of liver regeneration plays a protective role against hydrogen peroxide-induced oxidative stress in renal proximal tubule cells. Apoptosis 20(4):423–432.  https://doi.org/10.1007/s10495-015-1096-2 CrossRefPubMedGoogle Scholar
  20. 20.
    Liao XH, Zhang L, Liu Q, Sun H, Peng CM, Guo H (2010) Augmenter of liver regeneration protects kidneys from ischaemia/reperfusion injury in rats. Nephrol Dial Transplant 25(9):2921–2929.  https://doi.org/10.1093/ndt/gfq151 CrossRefPubMedGoogle Scholar
  21. 21.
    Liao XH, Zhang L, Tang XP, Liu Q, Sun H (2009) Expression of augmenter of liver regeneration in rats with gentamicin-induced acute renal failure and its protective effect on kidney. Ren Fail 31(10):946–955.  https://doi.org/10.3109/08860220903216154 CrossRefPubMedGoogle Scholar
  22. 22.
    Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 120(4):c179–184.  https://doi.org/10.1159/000339789 CrossRefPubMedGoogle Scholar
  23. 23.
    Aydin Z, van Zonneveld AJ, de Fijter JW, Rabelink TJ (2007) New horizons in prevention and treatment of ischaemic injury to kidney transplants. Nephrol Dial Transplant 22(2):342–346.  https://doi.org/10.1093/ndt/gfl690 CrossRefPubMedGoogle Scholar
  24. 24.
    Zweier JL, Talukder MA (2006) The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 70(2):181–190.  https://doi.org/10.1016/j.cardiores.2006.02.025 CrossRefPubMedGoogle Scholar
  25. 25.
    Sharfuddin AA, Molitoris BA (2011) Pathophysiology of ischemic acute kidney injury. Nat Rev Nephrol 7(4):189–200.  https://doi.org/10.1038/nrneph.2011.16 CrossRefPubMedGoogle Scholar
  26. 26.
    Yan R, Li Y, Zhang L, Xia N, Liu Q, Sun H, Guo H (2015) Augmenter of liver regeneration attenuates inflammation of renal ischemia/reperfusion injury through the NF-kappa B pathway in rats. Int Urol Nephrol 47(5):861–868.  https://doi.org/10.1007/s11255-015-0954-8 CrossRefPubMedGoogle Scholar
  27. 27.
    Wu CK, Dailey TA, Dailey HA, Wang BC, Rose JP (2003) The crystal structure of augmenter of liver regeneration: a mammalian FAD-dependent sulfhydryl oxidase. Protein Sci 12(5):1109–1118.  https://doi.org/10.1110/ps.0238103 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Sztolsztener ME, Brewinska A, Guiard B, Chacinska A (2013) Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. Traffic 14(3):309–320.  https://doi.org/10.1111/tra.12030 CrossRefPubMedGoogle Scholar
  29. 29.
    Funk JA, Schnellmann RG (2013) Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1alpha activation following ischemia-reperfusion injury. Toxicol Appl Pharmacol 273(2):345–354.  https://doi.org/10.1016/j.taap.2013.09.026 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Lynn EG, Stevens MV, Wong RP, Carabenciov D, Jacobson J, Murphy E, Sack MN (2010) Transient upregulation of PGC-1α diminishes cardiac ischemia tolerance via upregulation of ANT1. J Mol Cell Cardiol 49(4):693–698.  https://doi.org/10.1016/j.yjmcc.2010.06.008 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Jiang WG, Douglas-Jones A, Mansel RE (2003) Expression of peroxisome-proliferator activated receptor-gamma (PPARgamma) and the PPARgamma co-activator, PGC-1, in human breast cancer correlates with clinical outcomes. Int J Cancer 106(5):752–757.  https://doi.org/10.1002/ijc.11302 CrossRefPubMedGoogle Scholar
  32. 32.
    Choi HI, Kim HJ, Park JS, Kim IJ, Bae EH, Ma SK, Kim SW (2017) PGC-1alpha attenuates hydrogen peroxide-induced apoptotic cell death by upregulating Nrf-2 via GSK3beta inactivation mediated by activated p38 in HK-2 Cells. Sci Rep 7(1):4319.  https://doi.org/10.1038/s41598-017-04593-w CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88(2):611–638.  https://doi.org/10.1152/physrev.00025.2007 CrossRefPubMedGoogle Scholar
  34. 34.
    Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87(1):99–163.  https://doi.org/10.1152/physrev.00013.2006 CrossRefPubMedGoogle Scholar
  35. 35.
    Reel B, Guzeloglu M, Bagriyanik A, Atmaca S, Aykut K, Albayrak G, Hazan E (2013) The effects of PPAR-gamma agonist pioglitazone on renal ischemia/reperfusion injury in rats. J Surg Res 182(1):176–184.  https://doi.org/10.1016/j.jss.2012.08.020 CrossRefPubMedGoogle Scholar
  36. 36.
    Tang BL (2016) Sirt1 and the mitochondria. Mol Cells 39(2):87–95.  https://doi.org/10.14348/molcells.2016.2318 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Nephrology, The Second Affiliated HospitalChongqing Medical UniversityChongqingPeople’s Republic of China
  2. 2.Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingPeople’s Republic of China

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