Back to Journals » Drug Design, Development and Therapy » Volume 11

Humanin rescues cultured rat cortical neurons from NMDA-induced toxicity through the alleviation of mitochondrial dysfunction

Authors Cui A, Zhang Y, Li J, Song T, Liu X, Wang H, Zhang C, Ma G, Zhang H, Li K

Received 23 January 2017

Accepted for publication 15 March 2017

Published 18 April 2017 Volume 2017:11 Pages 1243—1253

DOI https://doi.org/10.2147/DDDT.S133042

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Rasika Samarasinghe

Peer reviewer comments 2

Editor who approved publication: Dr Sukesh Voruganti

Ai-Ling Cui,1 Ying-Hua Zhang,2 Jian-Zhong Li,3 Tianbin Song,4 Xue-Min Liu,1 Hui Wang,2 Ce Zhang,5 Guo-Lin Ma,6 Hui Zhang,7 Kefeng Li8

1Anatomy Department, Changzhi Medical College, Changzhi, Shanxi, 2Key Laboratory of Tissue Regeneration of Henan Province, Xinxiang Medical University, Xinxiang, Henan, 3Clinical Laboratory of Heji Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, 4Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 5Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, 6Department of Radiology, China-Japan Friendship Hospital, Beijing, 7Department of Radiology, First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 8School of Medicine, University of California – San Diego, San Diego, CA, USA

Abstract: N-methyl-D-aspartate (NDMA) receptor-mediated excitotoxicity has been implicated in a variety of pathological situations such as Alzheimer’s disease (AD) and Parkinson’s disease. However, no effective treatments for the same have been developed so far. Humanin (HN) is a 24-amino acid peptide originally cloned from the brain of patients with AD and it prevents stress-induced cell death in many cells/tissues. In our previous study, HN was found to effectively rescue rat cortical neurons. It is still not clear whether HN protects the neurons through the attenuation of mitochondrial dysfunction. In this study, excitatory toxicity was induced by NMDA, which binds the NMDA receptor in primarily cultured rat cortical neurons. We found that NMDA (100 µmol/L) dramatically induced the decrease of cell viability and caused mitochondrial dysfunction. Pretreatment of the neurons with HN (1 µmol/L) led to significant increases of mitochondrial succinate dehydrogenase (SDH) activity and membrane potential. In addition, HN pretreatment significantly reduced the excessive production of both reactive oxygen species (ROS) and nitric oxide (NO). Thus, HN could attenuate the excitotoxicity caused by the overactivation of the NMDA receptor through the alleviation of mitochondrial dysfunction.

Keywords: NMDA-induced toxicity, mitochondrial dysfunction, humanin, alleviation

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other articles by this author:

The regional neuronal activity in left posterior middle temporal gyrus is correlated with the severity of chronic aphasia

Li J, Du D, Gao W, Sun X, Xie H, Zhang G, Li J, Li H, Li K

Neuropsychiatric Disease and Treatment 2017, 13:1937-1945

Published Date: 20 July 2017

ROI for outlining an entire tumor is a reliable approach for quantification of lung cancer tumor vascular parameters using CT perfusion

Ma E, Ren A, Gao B, Yang M, Zhao Q, Wang W, Li K

OncoTargets and Therapy 2016, 9:2377-2384

Published Date: 27 April 2016

The reduction of volume and fiber bundle connections in the hippocampus of EGR3 transgenic schizophrenia rats

Ma E, Song T, Zhang H, Lu J, Wang L, Zhao Q, Guo R, Li M, Ma G, Lu G, Li K

Neuropsychiatric Disease and Treatment 2015, 11:1625-1638

Published Date: 1 July 2015