Display options
Cite
Zhang J, Xiang X, Shu S, et al. Advanced oxidation protein products inhibit the autophagy of renal tubular epithelial cells. Exp Ther Med. 2018;15(4):3908-3916doi: 10.3892/etm.2018.5875.
Zhang, J., Xiang, X., Shu, S., Zhang, C., Liang, Y., Jiang, T., Zhang, W., Guo, T., Liang, X., & Tang, X. (2018). Advanced oxidation protein products inhibit the autophagy of renal tubular epithelial cells. Experimental and therapeutic medicine, 15(4), 3908-3916. https://doi.org/10.3892/etm.2018.5875
Zhang, Jun, et al. "Advanced oxidation protein products inhibit the autophagy of renal tubular epithelial cells." Experimental and therapeutic medicine vol. 15,4 (2018): 3908-3916. doi: https://doi.org/10.3892/etm.2018.5875
Zhang J, Xiang X, Shu S, Zhang C, Liang Y, Jiang T, Zhang W, Guo T, Liang X, Tang X. Advanced oxidation protein products inhibit the autophagy of renal tubular epithelial cells. Exp Ther Med. 2018 Apr;15(4):3908-3916. doi: 10.3892/etm.2018.5875. Epub 2018 Feb 15. PMID: 29556265; PMCID: PMC5844045.
Copy Download .nbib Format: NLM
Share it on

Exp Ther Med. 2018 Apr;15(4):3908-3916. doi: 10.3892/etm.2018.5875. Epub 2018 Feb 15.

Advanced oxidation protein products inhibit the autophagy of renal tubular epithelial cells.

Experimental and therapeutic medicine

Jun Zhang, Xiaohong Xiang, Shuangshuang Shu, Cuiling Zhang, Yuling Liang, Tingting Jiang, Wenying Zhang, Tingting Guo, Xiujie Liang, Xun Tang

Affiliations

  1. Department of Nephrology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.

PMID: 29556265 PMCID: PMC5844045 DOI: 10.3892/etm.2018.5875

Abstract

It is well known that autophagy serves a crucial role in renal tubular epithelial cell (RTEC) injury in the pathogenesis of chronic kidney disease (CKD). The accumulation of advanced oxidation protein products (AOPPs) also participates in the progression of CKD. However, the effects of AOPPs on autophagy remain unknown. To clarify the underlying mechanism of RTEC injury in CKD, the effect of AOPPs on HK-2 cells, an RTEC cell line, was investigated. The results of the present study revealed that AOPP exposure downregulated the expression of B-cell lymphoma-2-interacting myosin-like coiled-coil protein 1, reduced the conversion of microtubule-associated proteins 1 light chain 3B (LC3)-I to LC3-II and the formation of autophagosomes, and lead to an accumulation of p62. These results suggest that AOPPs may inhibit the autophagic activity of HK-2 cells. Furthermore, the aforementioned changes were mediated by the AOPP-phosphorylated phosphoinositide 3-kinase3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway; this was verified by treatment with LY294002, a PI3K inhibitor, which reversed the AOPP-induced changes. The present study also demonstrated that the activation of autophagy with rapamycin led to an improvement in the AOPP-induced overexpression of kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin, two biomarkers of RTEC injury, whereas inhibiting autophagy with chloroquine further increased their expression during AOPP treatment. Collectively, these results indicate that AOPPs may inhibit autophagy in RTECs via activation of the PI3K/AKT/mTOR pathway and that autophagy inhibition serves a role in AOPP-induced RTEC injury.

Keywords: advanced oxidation protein products; autophagy; chronic kidney disease; phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway; renal tubular epithelial cell injury

References

  1. Exp Diabetes Res. 2011;2011:908185 - PubMed
  2. Physiol Res. 2002;51(6):597-604 - PubMed
  3. Adv Chronic Kidney Dis. 2005 Oct;12(4):353-65 - PubMed
  4. Cell Physiol Biochem. 2015;35(2):816-28 - PubMed
  5. Genes Dev. 2007 Nov 15;21(22):2861-73 - PubMed
  6. Kidney Int. 2012 Jul;82(2):172-83 - PubMed
  7. Kidney Int. 1996 May;49(5):1304-13 - PubMed
  8. Antioxid Redox Signal. 2014 Jan 20;20(3):519-37 - PubMed
  9. Kidney Int. 2011 Dec;80(12):1258-70 - PubMed
  10. Biochem Biophys Res Commun. 2008 Mar 28;368(1):100-6 - PubMed
  11. Nat Cell Biol. 2013 Jul;15(7):713-20 - PubMed
  12. Am J Physiol Renal Physiol. 2008 Apr;294(4):F777-87 - PubMed
  13. Nat Protoc. 2008;3(6):1101-8 - PubMed
  14. J Histochem Cytochem. 2013 Jun;61(6):433-43 - PubMed
  15. EMBO J. 2000 Nov 1;19(21):5720-8 - PubMed
  16. Nephrol Dial Transplant. 2014 Sep;29(9):1639-47 - PubMed
  17. Kidney Int. 2017 Jan;91(1):21-23 - PubMed
  18. J Am Soc Nephrol. 2013 Nov;24(11):1769-81 - PubMed
  19. Autophagy. 2012 Jul 1;8(7):1009-31 - PubMed
  20. Nephrol Dial Transplant. 2013 Nov;28 Suppl 4:iv29-36 - PubMed
  21. Nat Cell Biol. 2004 Dec;6(12 ):1221-8 - PubMed
  22. Am J Physiol Renal Physiol. 2012 Jul 15;303(2):F180-91 - PubMed
  23. Acta Pharmacol Sin. 2005 Dec;26(12 ):1421-34 - PubMed
  24. J Am Soc Nephrol. 2007 Feb;18(2):528-38 - PubMed
  25. J Immunol. 1998 Sep 1;161(5):2524-32 - PubMed
  26. Pharmacol Res Perspect. 2015 Jun;3(3):e00148 - PubMed
  27. Autophagy. 2012 Apr;8(4):445-544 - PubMed
  28. Methods Enzymol. 2009;452:181-97 - PubMed
  29. J Am Soc Nephrol. 2009 Dec;20(12):2493-502 - PubMed
  30. Cell Signal. 2014 Dec;26(12):2694-701 - PubMed
  31. Kidney Int. 2009 Dec;76(11):1148-60 - PubMed
  32. Lab Invest. 2014 Mar;94(3):309-20 - PubMed
  33. Dev Cell. 2004 Apr;6(4):463-77 - PubMed
  34. Autophagy. 2014 Feb;10(2):243-56 - PubMed

Publication Types