Humanin Rescues Cultured Rat Cortical Neurons from NMDA-Induced Toxicity Not by NMDA Receptor
Excitatory neurotoxicity has been implicated in many pathological situations and there is no effective treatment available. Humanin is a 24-aa peptide cloned from the brain of patients with Alzheimer’s disease (AD). In the present study, excitatory toxicity was induced by N-methyl-D-aspartate (NMDA)...
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2014-01-01
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Series: | The Scientific World Journal |
Online Access: | http://dx.doi.org/10.1155/2014/341529 |
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author | Ai-Ling Cui Jian-Zhong Li Zhi-Bo Feng Guo-Lin Ma Liang Gong Chun-Ling Li Ce Zhang Kefeng Li |
author_facet | Ai-Ling Cui Jian-Zhong Li Zhi-Bo Feng Guo-Lin Ma Liang Gong Chun-Ling Li Ce Zhang Kefeng Li |
author_sort | Ai-Ling Cui |
collection | DOAJ |
description | Excitatory neurotoxicity has been implicated in many pathological situations and there is no effective treatment available. Humanin is a 24-aa peptide cloned from the brain of patients with Alzheimer’s disease (AD). In the present study, excitatory toxicity was induced by N-methyl-D-aspartate (NMDA) in primarily cultured rat cortical neurons. MTT assessment, lactate dehydrogenase (LDH) release, and calcein staining were employed to evaluate the protective activity of humanin on NMDA induced toxicity. The results suggested that NMDA (100 μmol/L, 2.5 hr) triggered neuronal morphological changes, lactate dehydrogenase (LDH) release (166% of the control), reduction of cell viability (about 50% of the control), and the decrease of living cell density (about 50% of the control). When pretreated with humanin, the toxicity was suppressed. The living cells’ density of humanin treated group was similar to that of control. The cell viability was attenuated dose-dependently (IC50 = 0.132 nmol/L). The LDH release was also neutralized in a dose-dependent manner. In addition, the intracellular Ca2+ overloading triggered by NMDA reverted quickly and humanin could not inhibit it. These findings indicate that humanin can rescue cortical neurons from NMDA-induced toxicity in rat but not through interfering with NMDA receptor directly. |
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institution | Kabale University |
issn | 2356-6140 1537-744X |
language | English |
publishDate | 2014-01-01 |
publisher | Wiley |
record_format | Article |
series | The Scientific World Journal |
spelling | doaj-art-196cfc6279b04fe39dc6330d5dd384fa2025-02-03T01:02:16ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/341529341529Humanin Rescues Cultured Rat Cortical Neurons from NMDA-Induced Toxicity Not by NMDA ReceptorAi-Ling Cui0Jian-Zhong Li1Zhi-Bo Feng2Guo-Lin Ma3Liang Gong4Chun-Ling Li5Ce Zhang6Kefeng Li7Key Laboratory of Tissue Regeneration of Henan Province, Xinxiang Medical College, Eastern Part of Jinsui Road, Xinxiang, Henan 453003, ChinaClinical Laboratory of Heji Hospital Affiliated to Changzhi Medical College, 271 East Taihang Road, Changzhi, Shanxi 046000, ChinaKey Laboratory of Tissue Regeneration of Henan Province, Xinxiang Medical College, Eastern Part of Jinsui Road, Xinxiang, Henan 453003, ChinaDepartment of Radiology, China-Japan Friendship Hospital, Beijing 100029, ChinaKey Laboratory of Tissue Regeneration of Henan Province, Xinxiang Medical College, Eastern Part of Jinsui Road, Xinxiang, Henan 453003, ChinaKey Laboratory of Tissue Regeneration of Henan Province, Xinxiang Medical College, Eastern Part of Jinsui Road, Xinxiang, Henan 453003, ChinaDepartment of Physiology, Shanxi Medical University, No. 56 Xinjian Road, Taiyuan, Shanxi 030001, ChinaSchool of Medicine, University of California, San Diego (UCSD), San Diego, CA 92093, USAExcitatory neurotoxicity has been implicated in many pathological situations and there is no effective treatment available. Humanin is a 24-aa peptide cloned from the brain of patients with Alzheimer’s disease (AD). In the present study, excitatory toxicity was induced by N-methyl-D-aspartate (NMDA) in primarily cultured rat cortical neurons. MTT assessment, lactate dehydrogenase (LDH) release, and calcein staining were employed to evaluate the protective activity of humanin on NMDA induced toxicity. The results suggested that NMDA (100 μmol/L, 2.5 hr) triggered neuronal morphological changes, lactate dehydrogenase (LDH) release (166% of the control), reduction of cell viability (about 50% of the control), and the decrease of living cell density (about 50% of the control). When pretreated with humanin, the toxicity was suppressed. The living cells’ density of humanin treated group was similar to that of control. The cell viability was attenuated dose-dependently (IC50 = 0.132 nmol/L). The LDH release was also neutralized in a dose-dependent manner. In addition, the intracellular Ca2+ overloading triggered by NMDA reverted quickly and humanin could not inhibit it. These findings indicate that humanin can rescue cortical neurons from NMDA-induced toxicity in rat but not through interfering with NMDA receptor directly.http://dx.doi.org/10.1155/2014/341529 |
spellingShingle | Ai-Ling Cui Jian-Zhong Li Zhi-Bo Feng Guo-Lin Ma Liang Gong Chun-Ling Li Ce Zhang Kefeng Li Humanin Rescues Cultured Rat Cortical Neurons from NMDA-Induced Toxicity Not by NMDA Receptor The Scientific World Journal |
title | Humanin Rescues Cultured Rat Cortical Neurons from NMDA-Induced Toxicity Not by NMDA Receptor |
title_full | Humanin Rescues Cultured Rat Cortical Neurons from NMDA-Induced Toxicity Not by NMDA Receptor |
title_fullStr | Humanin Rescues Cultured Rat Cortical Neurons from NMDA-Induced Toxicity Not by NMDA Receptor |
title_full_unstemmed | Humanin Rescues Cultured Rat Cortical Neurons from NMDA-Induced Toxicity Not by NMDA Receptor |
title_short | Humanin Rescues Cultured Rat Cortical Neurons from NMDA-Induced Toxicity Not by NMDA Receptor |
title_sort | humanin rescues cultured rat cortical neurons from nmda induced toxicity not by nmda receptor |
url | http://dx.doi.org/10.1155/2014/341529 |
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