An Inhibitor of the Sodium–Hydrogen Exchanger-1 (NHE-1), Amiloride, Reduced Zinc Accumulation and Hippocampal Neuronal Death after Ischemia
Acidosis in the brain plays an important role in neuronal injury and is a common feature of several neurological diseases. It has been reported that the sodium–hydrogen exchanger-1 (NHE-1) is a key mediator of acidosis-induced neuronal injury. It modulates the concentration of intra- and extra-cellu...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/12/4232 |
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| author | Beom Seok Kang Bo Young Choi A Ra Kho Song Hee Lee Dae Ki Hong Jeong Hyun Jeong Dong Hyeon Kang Min Kyu Park Sang Won Suh |
| author_facet | Beom Seok Kang Bo Young Choi A Ra Kho Song Hee Lee Dae Ki Hong Jeong Hyun Jeong Dong Hyeon Kang Min Kyu Park Sang Won Suh |
| author_sort | Beom Seok Kang |
| collection | DOAJ |
| description | Acidosis in the brain plays an important role in neuronal injury and is a common feature of several neurological diseases. It has been reported that the sodium–hydrogen exchanger-1 (NHE-1) is a key mediator of acidosis-induced neuronal injury. It modulates the concentration of intra- and extra-cellular sodium and hydrogen ions. During the ischemic state, excessive sodium ions enter neurons and inappropriately activate the sodium–calcium exchanger (NCX). Zinc can also enter neurons through voltage-gated calcium channels and NCX. Here, we tested the hypothesis that zinc enters the intracellular space through NCX and the subsequent zinc accumulation induces neuronal cell death after global cerebral ischemia (GCI). Thus, we conducted the present study to confirm whether inhibition of NHE-1 by amiloride attenuates zinc accumulation and subsequent hippocampus neuronal death following GCI. Mice were subjected to GCI by bilateral common carotid artery (BCCA) occlusion for 30 min, followed by restoration of blood flow and resuscitation. Amiloride (10 mg/kg, intraperitoneally (<i>i.p.</i>)) was immediately injected, which reduced zinc accumulation and neuronal death after GCI. Therefore, the present study demonstrates that amiloride attenuates GCI-induced neuronal injury, likely via the prevention of intracellular zinc accumulation. Consequently, we suggest that amiloride may have a high therapeutic potential for the prevention of GCI-induced neuronal death. |
| first_indexed | 2024-03-10T19:11:20Z |
| format | Article |
| id | doaj.art-a4e53ae5511e4bcd86c8f0f787621ada |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:11:20Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a4e53ae5511e4bcd86c8f0f787621ada2023-11-20T03:46:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112423210.3390/ijms21124232An Inhibitor of the Sodium–Hydrogen Exchanger-1 (NHE-1), Amiloride, Reduced Zinc Accumulation and Hippocampal Neuronal Death after IschemiaBeom Seok Kang0Bo Young Choi1A Ra Kho2Song Hee Lee3Dae Ki Hong4Jeong Hyun Jeong5Dong Hyeon Kang6Min Kyu Park7Sang Won Suh8Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Medical Science, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaDepartment of Physiology, College of Medicine, Hallym University, Chuncheon 24252, KoreaAcidosis in the brain plays an important role in neuronal injury and is a common feature of several neurological diseases. It has been reported that the sodium–hydrogen exchanger-1 (NHE-1) is a key mediator of acidosis-induced neuronal injury. It modulates the concentration of intra- and extra-cellular sodium and hydrogen ions. During the ischemic state, excessive sodium ions enter neurons and inappropriately activate the sodium–calcium exchanger (NCX). Zinc can also enter neurons through voltage-gated calcium channels and NCX. Here, we tested the hypothesis that zinc enters the intracellular space through NCX and the subsequent zinc accumulation induces neuronal cell death after global cerebral ischemia (GCI). Thus, we conducted the present study to confirm whether inhibition of NHE-1 by amiloride attenuates zinc accumulation and subsequent hippocampus neuronal death following GCI. Mice were subjected to GCI by bilateral common carotid artery (BCCA) occlusion for 30 min, followed by restoration of blood flow and resuscitation. Amiloride (10 mg/kg, intraperitoneally (<i>i.p.</i>)) was immediately injected, which reduced zinc accumulation and neuronal death after GCI. Therefore, the present study demonstrates that amiloride attenuates GCI-induced neuronal injury, likely via the prevention of intracellular zinc accumulation. Consequently, we suggest that amiloride may have a high therapeutic potential for the prevention of GCI-induced neuronal death.https://www.mdpi.com/1422-0067/21/12/4232global cerebral ischemiaamiloridesodium–hydrogen exchanger-1zincneuronal deathneuroprotection |
| spellingShingle | Beom Seok Kang Bo Young Choi A Ra Kho Song Hee Lee Dae Ki Hong Jeong Hyun Jeong Dong Hyeon Kang Min Kyu Park Sang Won Suh An Inhibitor of the Sodium–Hydrogen Exchanger-1 (NHE-1), Amiloride, Reduced Zinc Accumulation and Hippocampal Neuronal Death after Ischemia International Journal of Molecular Sciences global cerebral ischemia amiloride sodium–hydrogen exchanger-1 zinc neuronal death neuroprotection |
| title | An Inhibitor of the Sodium–Hydrogen Exchanger-1 (NHE-1), Amiloride, Reduced Zinc Accumulation and Hippocampal Neuronal Death after Ischemia |
| title_full | An Inhibitor of the Sodium–Hydrogen Exchanger-1 (NHE-1), Amiloride, Reduced Zinc Accumulation and Hippocampal Neuronal Death after Ischemia |
| title_fullStr | An Inhibitor of the Sodium–Hydrogen Exchanger-1 (NHE-1), Amiloride, Reduced Zinc Accumulation and Hippocampal Neuronal Death after Ischemia |
| title_full_unstemmed | An Inhibitor of the Sodium–Hydrogen Exchanger-1 (NHE-1), Amiloride, Reduced Zinc Accumulation and Hippocampal Neuronal Death after Ischemia |
| title_short | An Inhibitor of the Sodium–Hydrogen Exchanger-1 (NHE-1), Amiloride, Reduced Zinc Accumulation and Hippocampal Neuronal Death after Ischemia |
| title_sort | inhibitor of the sodium hydrogen exchanger 1 nhe 1 amiloride reduced zinc accumulation and hippocampal neuronal death after ischemia |
| topic | global cerebral ischemia amiloride sodium–hydrogen exchanger-1 zinc neuronal death neuroprotection |
| url | https://www.mdpi.com/1422-0067/21/12/4232 |
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