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5-Hydroxytryptophan (5-HTP)-induced intracellular syndrome in mouse non-neural embryonic cells is associated with inhibited proliferation and cell death.

Abstract：

: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. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Gordeeva O,Safandeev V

doi

10.1016/j.neuropharm.2019.107862

subject

Has Abstract

pub_date

2019-11-25 00:00:00

pages

107862

eissn

0028-3908

issn

1873-7064

pii

S0028-3908(19)30428-9

pub_type

杂志文章

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5-Hydroxytryptophan (5-HTP)-induced intracellular syndrome in mouse non-neural embryonic cells is associated with inhibited proliferation and cell death.