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Journal of cellular and molecular medicine
05, 2019;23 (5): 3429-3440.

Acid-sensing ion channel 1a is involved in ischaemia/reperfusion induced kidney injury by increasing renal epithelia cell apoptosis.

Nana Song, Zhihui Lu, Jian Zhang, Yiqin Shi, Yichun Ning, Jing Chen, Shi Jin, Bo Shen, Yi Fang, Jianzhou Zou, Jie Teng, Xiang-Ping Chu, Linlin Shen, Xiaoqiang Ding
Author Information
  1. Nana Song: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China. ORCID
  2. Zhihui Lu: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  3. Jian Zhang: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  4. Yiqin Shi: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  5. Yichun Ning: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  6. Jing Chen: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  7. Shi Jin: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  8. Bo Shen: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  9. Yi Fang: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  10. Jianzhou Zou: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  11. Jie Teng: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  12. Xiang-Ping Chu: Department of Biomedical Sciences, School of Medicine, University of Missouri -Kansas City, Missouri.
  13. Linlin Shen: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
  14. Xiaoqiang Ding: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
PMID: 30793492 DOI: 10.1111/jcmm.14238

Abstract

Acidic microenvironment is commonly observed in ischaemic tissue. In the kidney, extracellular pH dropped from 7.4 to 6.5 within 10 minutes initiation of ischaemia. Acid-sensing ion channels (ASICs) can be activated by pH drops from 7.4 to 7.0 or lower and permeates to Ca entrance. Thus, activation of ASIC1a can mediate the intracellular Ca accumulation and play crucial roles in apoptosis of cells. However, the role of ASICs in renal ischaemic injury is unclear. The aim of the present study was to test the hypothesis that ischaemia increases renal epithelia cell apoptosis through ASIC1a-mediated calcium entry. The results show that ASIC1a distributed in the proximal tubule with higher level in the renal tubule ischaemic injury both in vivo and in vitro. In vivo, Injection of ASIC1a inhibitor PcTx-1 previous to ischaemia/reperfusion (I/R) operation attenuated renal ischaemic injury. In vitro, HK-2 cells were pre-treated with PcTx-1 before hypoxia, the intracellular concentration of Ca , mitochondrial transmembrane potential (∆ψm) and apoptosis was measured. Blocking ASIC1a attenuated I/R induced Ca overflow, loss of ∆ψm and apoptosis in HK-2 cells. The results revealed that ASIC1a localized in the proximal tubular and contributed to I/R induced kidney injury. Consequently, targeting the ASIC1a may prove to be a novel strategy for AKI patients.

Keywords

acid-sensing ion channels apoptosis calcium ischaemia/reperfusion injury kidney mitochondrial transmembrane potential

References

  1. Biores Open Access. 2018 Feb 01;7(1):2-9 [PMID: 29445584]
  2. PLoS One. 2012;7(7):e39982 [PMID: 22792205]
  3. Am J Physiol Renal Physiol. 2016 Jul 1;311(1):F145-61 [PMID: 27194714]
  4. Am J Physiol Renal Physiol. 2018 Apr 1;314(4):F584-F601 [PMID: 29357442]
  5. Expert Opin Ther Targets. 2014 Jan;18(1):1-14 [PMID: 24261866]
  6. Cell. 2004 Sep 17;118(6):687-98 [PMID: 15369669]
  7. Mol Vis. 2011;17:3300-8 [PMID: 22194656]
  8. Med Sci Monit. 2017 Apr 21;23:1916-1922 [PMID: 28428534]
  9. Brain. 2007 Jan;130(Pt 1):151-8 [PMID: 17114797]
  10. Mol Cell Biochem. 2010 Jul;340(1-2):153-9 [PMID: 20179994]
  11. J Pharmacol Exp Ther. 2008 Nov;327(2):491-502 [PMID: 18723775]
  12. Inflamm Res. 2012 Apr;61(4):327-35 [PMID: 22237475]
  13. Stem Cells Int. 2017;2017:7168687 [PMID: 28194187]
  14. Wiley Interdiscip Rev Membr Transp Signal. 2012;1(5):655-662 [PMID: 23181201]
  15. Transl Stroke Res. 2014 Feb;5(1):59-68 [PMID: 24390970]
  16. Mol Cell Biochem. 2018 Jun;443(1-2):81-91 [PMID: 29086909]
  17. J Biol Chem. 2016 Aug 26;291(35):18370-83 [PMID: 27402850]
  18. Am J Kidney Dis. 2012 Mar;59(3):452-61 [PMID: 22277744]
  19. Klin Wochenschr. 1988 Sep 15;66(18):800-7 [PMID: 2846945]
  20. Biochem Soc Trans. 2006 Dec;34(Pt 6):1356-61 [PMID: 17073818]
  21. Cell Calcium. 2010 Jul;48(1):70-82 [PMID: 20678793]
  22. Int Immunopharmacol. 2015 Dec;29(2):748-760 [PMID: 26359543]
  23. J Am Soc Nephrol. 2006 Jan;17(1):39-45 [PMID: 16319186]
  24. Onco Targets Ther. 2015 Aug 14;8:2121-7 [PMID: 26316781]
  25. Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1527-32 [PMID: 24127583]
  26. Magn Reson Med. 2012 Aug;68(2):649-55 [PMID: 22162021]
  27. Am J Physiol Renal Physiol. 2013 Apr 15;304(8):F1066-75 [PMID: 23389456]
  28. Am J Physiol Renal Physiol. 2009 Oct;297(4):F1006-16 [PMID: 19640902]
  29. PLoS One. 2014 Oct 24;9(10):e110944 [PMID: 25343248]
  30. J Cell Mol Med. 2019 May;23(5):3429-3440 [PMID: 30793492]
  31. Am J Physiol Renal Physiol. 2008 Aug;295(2):F534-44 [PMID: 18495803]
  32. Anat Rec (Hoboken). 2018 Feb 20;301(7):1179-1188 [PMID: 29461680]
  33. Recent Pat Biotechnol. 2015;9(1):30-41 [PMID: 26563811]
  34. Cell Calcium. 2010 Feb;47(2):122-9 [PMID: 20167368]
  35. Behav Brain Res. 2018 Jan 30;337:246-251 [PMID: 28912013]
  36. Transplantation. 2003 Mar 27;75(6):744-9 [PMID: 12660495]
  37. Curr Eye Res. 2018 Jul;43(7):921-933 [PMID: 29595330]
  38. Neuropharmacology. 2015 Jul;94:9-18 [PMID: 25585135]
  39. Acta Pharmacol Sin. 2007 Oct;28(10):1621-7 [PMID: 17883949]
  40. Prog Neurobiol. 2014 Apr;115:189-209 [PMID: 24467911]
  41. J Am Soc Nephrol. 2012 Apr;23(4):674-86 [PMID: 22343121]
  42. Neuropharmacology. 2015 Dec;99:650-7 [PMID: 26320544]
  43. Sci Rep. 2017 Mar 23;7:44951 [PMID: 28332558]
  44. Sci Rep. 2016 Dec 09;6:38777 [PMID: 27934921]
  45. Am J Physiol Renal Physiol. 2008 Oct;295(4):F912-22 [PMID: 18701635]

MeSH Term

Acid Sensing Ion Channels
Animals
Apoptosis
Calcium
Caspase 3
Cell Hypoxia
Cell Line
Epithelial Cells
Humans
Intracellular Space
Kidney
Kidney Tubules
Male
Membrane Potential, Mitochondrial
Mice, Inbred C57BL
Models, Biological
Peptides
Reperfusion Injury
Spider Venoms

Chemicals

Acid Sensing Ion Channels
PcTX1 protein, Psalmopoeus cambridgei
Peptides
Spider Venoms
Caspase 3
Calcium
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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