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5-Hydroxytryptophan (5-HTP)-induced intracellular syndrome in mouse non-neural embryonic cells is associated with inhibited proliferation and cell deathстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Gordeeva O.F., Safandeev V.V.
- Журнал: Neuropharmacology
- Год издания: 2019
- Издательство: Pergamon Press Ltd.
- Местоположение издательства: United Kingdom
- DOI: 10.1016/j.neuropharm.2019.107862
- Аннотация: 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 serotonin 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 serotonin 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 serotonin-mediated protein modifications.
- Добавил в систему: Сафандеев Виталий Васильевич