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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Main Authors: Ai-Ling Cui, Jian-Zhong Li, Zhi-Bo Feng, Guo-Lin Ma, Liang Gong, Chun-Ling Li, Ce Zhang, Kefeng Li
Format: Article
Language:English
Published: Wiley 2014-01-01
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
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publishDate 2014-01-01
publisher Wiley
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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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