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Excessive apoptosis and ROS induced by ethionine affect neural cell viability and differentiation.
- Source :
-
Acta biochimica et biophysica Sinica [Acta Biochim Biophys Sin (Shanghai)] 2020 Oct 19; Vol. 52 (10), pp. 1156-1165. - Publication Year :
- 2020
-
Abstract
- The central nervous system (CNS) diseases are still a major cause of morbidity and mortality throughout the world, which imposes heavy burden on the development of society. Ethionine is a non-proteinogenic amino acid having similar chemical structure and activity to that of methionine, with which it competes. Previous studies have confirmed that ethionine affects various cellular functions by inhibiting the biosynthesis of proteins, RNA, DNA, and phospholipids, or all of them. The relationship of ethionine with some CNS diseases, including neural tube defects, has been investigated recently. However, the detailed effects of ethionine on the nerve cell bioactivities and the underlying mechanisms have not been fully explored. Herein, we systematically investigated the influences of ethionine on the proliferation, differentiation, and apoptosis of neural stem cells (NSCs) and post-mitotic nerve cells. We demonstrated that ethionine inhibited cell viability by disrupting the balance between proliferation and apoptosis, prevented NSCs from differentiating into neurons and astrocytes, and blocked cell progression from G1 to S phase via reducing cyclin D1 function in nerve cells including NSCs, a mouse hippocampal neuron cell line (HT-22), and a mouse brain neuroma cell line (Neuro-2a). We speculated that the inhibitory effect of ethionine on cell viability and differentiation are associated with increased reactive oxygen species production. Our results also supported the concept that ethionine may be an underlying cause of abnormal folate metabolism-induced CNS diseases. Our findings may provide important direction for the application of abnormal folate metabolism-induced CNS diseases in future NSC-based therapies.<br /> (© The Author(s) 2020. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Astrocytes metabolism
Caspase 3 metabolism
Cell Cycle drug effects
Cell Proliferation drug effects
Cells, Cultured
Central Nervous System Diseases etiology
Central Nervous System Diseases metabolism
Cyclin D1 metabolism
Dose-Response Relationship, Drug
Mice
Neural Stem Cells cytology
Neural Stem Cells metabolism
Neurons metabolism
bcl-2-Associated X Protein metabolism
Apoptosis drug effects
Cell Differentiation drug effects
Cell Survival drug effects
Ethionine pharmacology
Neural Stem Cells drug effects
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1745-7270
- Volume :
- 52
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Acta biochimica et biophysica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- 33083831
- Full Text :
- https://doi.org/10.1093/abbs/gmaa093