Advertisement

Apoptosis

pp 1–12 | Cite as

Overexpression of augmenter of liver regeneration (ALR) mitigates the effect of H2O2-induced endoplasmic reticulum stress in renal tubule epithelial cells

  • Xiao Jiang
  • Xiao-hui Liao
  • Li-li Huang
  • Hang Sun
  • Qi Liu
  • Ling ZhangEmail author
Article
  • 58 Downloads

Abstract

Ischemia/reperfusion is a major cause of acute kidney injury and can induce apoptosis in renal epithelial tubule (HK-2) cells. Accumulating evidence indicates that endoplasmic reticulum (ER) stress is a major contributor to apoptosis in acute kidney injury. We previously reported that augmenter of liver regeneration (ALR) functions as an anti-apoptotic factor in H2O2-treated HK-2 cells although the precise mechanism underlying this action remains unclear. In the present study, we investigate the role of ALR in H2O2-induced ER stress-mediated apoptosis. We overexpressed ALR and established a H2O2-induced ER stress model in HK-2 cells. Overexpression of ALR reduced the level of reactive oxygen species and the rate of apoptosis in H2O2-treated HK-2 cells. Using confocal microscopy and western blot, we observed that ALR colocalized with the ER and mitochondria compartment. Moreover, ALR suppressed ER stress by maintaining the morphology of the ER and reducing the levels of the ER-related proteins, glucose-regulated protein 78 (GRP78), phospho-protein kinase-like ER kinase (p-PERK), phospho-eukaryotic initiation factor 2α (p-eIF2α) and C/EBP-homologous protein (CHOP) significantly (p < 0.05). Mechanistically, ALR promoted Bcl-2 expression and suppressed Bax and cleaved-caspase-3 expression significantly during ER-stress induced apoptosis (p < 0.05). Furthermore, ALR attenuated calcium release from the ER, and transfer to mitochondria, under ER stress. To conclude, ALR alleviates H2O2-induced ER stress-mediated apoptosis in HK-2 cells by suppressing ER stress response and by maintaining calcium homeostasis. Consequently, ALR may protect renal tubule epithelial cells from ischemia/reperfusion induced acute kidney injury.

Keywords

Augmenter of liver regeneration Endoplasmic reticulum stress Apoptosis Acute kidney injury 

Notes

Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81873604 and 30971334), Natural Science Foundation Project of CQ CSTC (Grant No. cstc2015jcyjA10069), Medical Scientific Research Projects of Chongqing Health and Family Planning Commission (Grant No. 20142031) and The Found for Fostering Talents in Scientific Research of Chongqing Medical University (Grant No. 201404).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Zuk A, Bonventre JV (2016) Acute kidney injury. Annu Rev Med 67(1):293–307.  https://doi.org/10.1146/annurev-med-050214-013407 Google Scholar
  2. 2.
    Bellomo R, Kellum JA, Ronco C (2012) Acute kidney injury. Lancet 380(9843):756–766.  https://doi.org/10.1016/s0140-6736(11)61454-2 Google Scholar
  3. 3.
    Arai S, Kitada K, Yamazaki T, Takai R, Zhang X, Tsugawa Y, Sugisawa R, Matsumoto A, Mori M, Yoshihara Y, Doi K, Maehara N, Kusunoki S, Takahata A, Noiri E, Suzuki Y, Yahagi N, Nishiyama A, Gunaratnam L, Takano T, Miyazaki T (2016) Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice. Nat Med 22:183.  https://doi.org/10.1038/nm.4012 Google Scholar
  4. 4.
    Basile DP, Anderson MD, Sutton TA (2012) Pathophysiology of acute kidney injury. Compr Physiol 2(2):1303–1353.  https://doi.org/10.1002/cphy.c110041 Google Scholar
  5. 5.
    Dennis MJ, Witting KP (2017) Protective role for antioxidants in acute kidney disease. Nutrients.  https://doi.org/10.3390/nu9070718 Google Scholar
  6. 6.
    Ali I, Shah SZ, Jin Y, Li ZS, Ullah O, Fang NZ (2017) Reactive oxygen species-mediated unfolded protein response pathways in preimplantation embryos. J Vet Sci 18(1):1–9.  https://doi.org/10.4142/jvs.2017.18.1.1 Google Scholar
  7. 7.
    Qin C, Xiao C, Su Y, Zheng H, Xu T, Lu J, Luo P, Zhang J (2017) Tisp40 deficiency attenuates renal ischemia reperfusion injury induced apoptosis of tubular epithelial cells. Exp Cell Res 359(1):138–144.  https://doi.org/10.1016/j.yexcr.2017.07.038 Google Scholar
  8. 8.
    Noh MR, Kim JI, Han SJ, Lee TJ, Park KM (2015) C/EBP homologous protein (CHOP) gene deficiency attenuates renal ischemia/reperfusion injury in mice. Biochim Biophys Acta 1852(9):1895–1901.  https://doi.org/10.1016/j.bbadis.2015.06.004 Google Scholar
  9. 9.
    Chen BL, Sheu ML, Tsai KS, Lan KC, Guan SS, Wu CT, Chen LP, Hung KY, Huang JW, Chiang CK, Liu SH (2015) CCAAT-enhancer-binding protein homologous protein deficiency attenuates oxidative stress and renal ischemia-reperfusion injury. Antioxid Redox Signal 23(15):1233–1245.  https://doi.org/10.1089/ars.2013.5768 Google Scholar
  10. 10.
    Bravo-Sagua R, Rodriguez AE, Kuzmicic J, Gutierrez T, Lopez-Crisosto C, Quiroga C, Diaz-Elizondo J, Chiong M, Gillette TG, Rothermel BA, Lavandero S (2013) Cell death and survival through the endoplasmic reticulum-mitochondrial axis. Curr Mol Med 13(2):317–329.  https://doi.org/10.2174/1566524011313020008 Google Scholar
  11. 11.
    Oyadomari S, Mori M (2003) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11:381.  https://doi.org/10.1038/sj.cdd.4401373 Google Scholar
  12. 12.
    Zhou X, Hao W, Shi H, Hou Y, Xu Q (2015) Calcium homeostasis disruption—a bridge connecting cadmium-induced apoptosis, autophagy and tumorigenesis. Oncol Res Treat 38(6):311–315Google Scholar
  13. 13.
    Pinton P, Giorgi C, Siviero R, Zecchini E, Rizzuto R (2008) Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene 27:6407.  https://doi.org/10.1038/onc.2008.308 Google Scholar
  14. 14.
    Rizzuto R, Marchi S, Bonora M, Aguiari P, Bononi A, De Stefani D, Giorgi C, Leo S, Rimessi A, Siviero R, Zecchini E, Pinton P (2009) Ca2+ transfer from the ER to mitochondria: when, how and why. Biochim Biophys Acta (BBA) Bioenergetics 1787(11):1342–1351.  https://doi.org/10.1016/j.bbabio.2009.03.015 Google Scholar
  15. 15.
    Nalesnik MA, Gandhi CR, Starzl TE (2017) Augmenter of liver regeneration: a fundamental life protein. Hepatology 66(1):266–270.  https://doi.org/10.1002/hep.29047 Google Scholar
  16. 16.
    Hagiya M, Fracavailla A, Polimeno L, Ihara I, Sakai H, Seki T, Shimonishi M, Porter KA, Starzl TE (1994) Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombinant ALR and demonstration of tissue distribution. Proc Natl Acad Sci USA 91(17):8142–8146Google Scholar
  17. 17.
    Liao X-h, Zhang L, Liu Q, Sun H, Peng C-m, Guo H et al (2010) Augmenter of liver regeneration protects kidneys from ischaemia/reperfusion injury in ratsX. Nephrol Dial Transplant 25(9):2921–2929.  https://doi.org/10.1093/ndt/gfq151 Google Scholar
  18. 18.
    Tury A, Mairet-Coello G, Lisowsky T, Griffond B, Fellmann D (2005) Expression of the sulfhydryl oxidase ALR (augmenter of liver regeneration) in adult rat brain. Brain Res.  https://doi.org/10.1016/j.brainres.2005.04.050 Google Scholar
  19. 19.
    Gandhi CR (2012) Augmenter of liver regeneration. Fibrogenes Tissue Repair 5(1):10.  https://doi.org/10.1186/1755-1536-5-10 Google Scholar
  20. 20.
    Lange H, Lisowsky T, Gerber J, Mühlenhoff U, Kispal G, Lill R (2001) An essential function of the mitochondrial sulfhydryl oxidase Erv1p/ALR in the maturation of cytosolic Fe/S proteins. EMBO Rep.  https://doi.org/10.1093/embo-reports/kve161 Google Scholar
  21. 21.
    Sevier CS, Cuozzo JW, Vala A, Åslund F, Kaiser CA (2001) A flavoprotein oxidase defines a new endoplasmic reticulum pathway for biosynthetic disulphide bond formation. Nat Cell Biol 3:874.  https://doi.org/10.1038/ncb1001-874 Google Scholar
  22. 22.
    Polimeno L, Pesetti B, De Santis F, Resta L, Rossi R, De Palma A, Girardi B, Amoruso A, Francavilla A (2012) Decreased expression of the augmenter of liver regeneration results in increased apoptosis and oxidative damage in human-derived glioma cells. Cell Death Dis 3:e289.  https://doi.org/10.1038/cddis.2012.25 Google Scholar
  23. 23.
    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 Int J Progr Cell Death 20(4):423–432.  https://doi.org/10.1007/s10495-015-1096-2 Google Scholar
  24. 24.
    Liu XR, Cao L, Li T, Chen LL, Yu YY, Huang WJ, Liu L, Tan XQ (2017) Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes. Apoptosis Int J Progr Cell Death 22(5):639–646.  https://doi.org/10.1007/s10495-017-1349-3 Google Scholar
  25. 25.
    Hajnóczky G, Robb-Gaspers LD, Seitz MB, Thomas AP (1995) Decoding of cytosolic calcium oscillations in the mitochondria. Cell 82(3):415–424.  https://doi.org/10.1016/0092-8674(95)90430-1 Google Scholar
  26. 26.
    Babcock DF, Herrington J, Goodwin PC, Park YB, Hille B (1997) Mitochondrial participation in the intracellular Ca2+ network. J Cell Biol 136(4):833Google Scholar
  27. 27.
    Bonventre JV, Yang L (2011) Cellular pathophysiology of ischemic acute kidney injury. J Clin Investig 121(11):4210–4221.  https://doi.org/10.1172/JCI45161 Google Scholar
  28. 28.
    Boussabbeh M, Ben Salem I, Prola A, Guilbert A, Bacha H, Abid-Essefi S, Lemaire C (2015) Patulin induces apoptosis through ROS-mediated endoplasmic reticulum stress pathway. Toxicol Sci 144(2):328–337.  https://doi.org/10.1093/toxsci/kfu319 Google Scholar
  29. 29.
    Pluquet O, Pourtier A, Abbadie C (2015) The unfolded protein response and cellular senescence. A review in the theme: cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. Am J Physiol Cell Physiol 308(6):C415–C425.  https://doi.org/10.1152/ajpcell.00334.2014 Google Scholar
  30. 30.
    Zhu G, Lee AS (2015) Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. J Cell Physiol 230(7):1413–1420.  https://doi.org/10.1002/jcp.24923 Google Scholar
  31. 31.
    Fu XL, Gao DS (2014) Endoplasmic reticulum proteins quality control and the unfolded protein response: the regulative mechanism of organisms against stress injuries. BioFactors 40(6):569–585.  https://doi.org/10.1002/biof.1194 Google Scholar
  32. 32.
    Taniguchi M, Yoshida H (2015) Endoplasmic reticulum stress in kidney function and disease. Curr Opin Nephrol Hypertens 24(4):345–350.  https://doi.org/10.1097/MNH.0000000000000141 Google Scholar
  33. 33.
    Verfaillie T, Rubio N, Garg AD, Bultynck G, Rizzuto R, Decuypere JP, Piette J, Linehan C, Gupta S, Samali A, Agostinis P (2012) PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ 19(11):1880–1891.  https://doi.org/10.1038/cdd.2012.74 Google Scholar
  34. 34.
    Wu C-C, Bratton SB (2012) Regulation of the intrinsic apoptosis pathway by reactive oxygen species. Antioxid Redox Signal 19(6):546–558.  https://doi.org/10.1089/ars.2012.4905 Google Scholar
  35. 35.
    Iurlaro R, Muñoz-Pinedo C (2015) Cell death induced by endoplasmic reticulum stress. FEBS J 283(14):2640–2652.  https://doi.org/10.1111/febs.13598 Google Scholar
  36. 36.
    Sano R, Reed JC (2013) ER stress-induced cell death mechanisms. Biochim Biophys Acta 1833(12):3460–3470.  https://doi.org/10.1016/j.bbamcr.2013.06.028 Google Scholar
  37. 37.
    Qiao Y, Wang C, Xu K, Meng L, Li X, Pei X, Wang J, Meng H, Zeng L (2014) Changes in calcium/calmodulin level and mitochondrial membrane potential in cochlear neurons of newborn mice infected with murine cytomegalovirus. Cell Biochem Biophys 69(3):593–598.  https://doi.org/10.1007/s12013-014-9838-2 Google Scholar
  38. 38.
    Deniaud A, Sharaf el dein O, Maillier E, Poncet D, Kroemer G, Lemaire C, Brenner C (2008) Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis. Oncogene 27(3):285–299.  https://doi.org/10.1038/sj.onc.1210638 Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NephrologySecond Affiliated Hospital of Chongqing Medical UniversityChongqingChina
  2. 2.Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious DiseasesSecond Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Personalised recommendations