5-Hydroxytryptophan (5-HTP)-induced intracellular syndrome in mouse non-neural embryonic cells is associated with inhibited proliferation and cell death
| Autor: | O. F. Gordeeva, Vitaliy Safandeev |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Serotonin Programmed cell death Somatic cell Apoptosis 3T3 cells 5-Hydroxytryptophan Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Extracellular medicine Animals Annexin A5 Cell Proliferation Pharmacology Cell Death Cell growth Chemistry Mouse Embryonic Stem Cells Cell cycle Alkaline Phosphatase Embryonic stem cell Cell biology 030104 developmental biology medicine.anatomical_structure NIH 3T3 Cells 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Neuropharmacology. 195:107862 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2019.107862 |
| Popis: | Biogenic monoamines are involved in the regulation of various processes in both neural and non-neural cells during development. The present study aimed to identify the regulatory effects of serotonin (5-HT) and its precursors ( l -tryptophan and 5-hydroxytryptophan, 5-HTP) on proliferation and cell death in mouse embryonic stem cells (ESCs) and embryonic fibroblasts (MEFs and 3T3 cells). The concentration-dependent cell growth and viability of the ESCs, MEFs and 3T3 cells were analyzed after treatment with l -tryptophan, 5-HTP and 5-HT in the concentration range 10−6 - 10−2 M. Treating the cells with 5-HTP, but not l -tryptophan and 5-HT, induced reversible toxic effects. 5-HTP treatment (10−3 - 10−2 M) significantly inhibited cell proliferation through blocking of the S-phase of the cell cycle and increasing apoptotic and necrotic cell death. Moreover, 5-HTP treatment stimulated a reorganization of the actin and tubulin networks and upregulated the gene expression of enzymes involved in 5-HT synthesis and metabolism: aromatic amino acid decarboxylase (Aadc/Ddc), monoamine oxidase A (Maoa), and transglutaminase 2 (Tgm2). HPLC analysis found no changes in the intracellular and extracellular levels of 5-HT after 5-HTP treatment, but a significant increase of intracellular 5-HTP levels. However, inhibition of AADC with NSD-1015 or transglutaminase with cystamine prevented 5-HTP-induced cell growth impairment and attenuated the toxic effects of 5-HTP treatment. Our results suggest that 5-HTP can induce toxic effects through cell cycle arrest and cell death in embryonic stem and somatic cells by enhancing the levels of 5-HT-mediated protein modifications. This article is part of the special issue entitled ‘Serotonin Research: Crossing Scales and Boundaries’. |
| Databáze: | OpenAIRE |
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