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Published on: September 9, 2020
Glutaric acid-mediated apoptosis in primary striatal neurons
Fengyan Tian1, Xi Fu2, Jinzhi Gao2
1Department 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.
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.
