Glutaric Acid-Mediated Apoptosis in Primary Striatal Neurons

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BioMed Research InternationalVolume 2014 2014, Article ID 484731, 10 pages
Research Article
Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Laboratory of Infectious Immunology, Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Received 12 February 2014; Revised 20 April 2014; Accepted 21 April 2014; Published 12 May 2014
Academic Editor: Janet K. Kern
Copyright © 2014 Fengyan Tian et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Glutaric acid GA has been implicated in the mechanism of neurodegeneration in glutaric aciduria type I. In the present study, the potential cytotoxic effects of GA 0.1~50 mM for 24~96 h were examined in cultured primary rat striatal neurons. Results showed increase in the number of cells labeled by annexin-V or with apoptotic features shown by Hoechst-PI staining and transmission electron microscopy TEM and upregulation of the expression of mRNA as well as the active protein fragments caspase 3, suggesting involvement of the caspase 3-dependent apoptotic pathway in GA-induced striatal neuronal death. This effect was in part suppressed by the N-methyl-D-aspartate NMDA receptor antagonist MK-801 but not the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid AMPA antagonist 6-cyano-7-nitroquinoxalone-2,3-dione CNQX. Thus, GA may trigger neuronal damage partially through apoptotic pathway and via activation of NMDA receptors in cultured primary striatal neurons.
Autor: Fengyan Tian, Xi Fu, Jinzhi Gao, Yanqin Ying, Ling Hou, Yan Liang, Qin Ning, and Xiaoping Luo
Fuente: https://www.hindawi.com/