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J Cell Mol Med. 2019 Feb 22. doi: 10.1111/jcmm.14238. [Epub ahead of print]

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

Song N1,2,3,4,5, Lu Z1,2,3,4,5, Zhang J1,2,3,4,5, Shi Y1,2,3,4,5, Ning Y1,2,3,4,5, Chen J1,2,3,4,5, Jin S1,2,3,4,5, Shen B1,2,3,4,5, Fang Y1,2,3,4,5, Zou J1,2,3,4,5, Teng J1,2,3,4,5, Chu XP6, Shen L7, Ding X1,2,3,4,5.

Author information

1
Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
2
Shanghai Medical Center of Kidney, Shanghai, China.
3
Shanghai Institute of Kidney and Dialysis, Shanghai, China.
4
Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China.
5
Hemodialysis quality control center of Shanghai, Shanghai, China.
6
Department of Biomedical Sciences, School of Medicine, University of Missouri -Kansas City, Missouri.
7
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

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 Ca2+ entrance. Thus, activation of ASIC1a can mediate the intracellular Ca2+ 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 Ca2+ , mitochondrial transmembrane potential (∆ψm) and apoptosis was measured. Blocking ASIC1a attenuated I/R induced Ca2+ 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

PMID:
30793492
DOI:
10.1111/jcmm.14238
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