The Effect of the Stress Induced by Hydrogen Peroxide and Corticosterone on Tryptophan Metabolism, Using Human Neuroblastoma Cell Line (SH-SY5Y)

Int J Mol Sci. 2023 Feb 23;24(5):4389. doi: 10.3390/ijms24054389.

Abstract

L-tryptophan (L-Trp) is an important amino acid in several physiological mechanisms, being metabolized into two important pathways: the kynurenine and the serotonin (5-HT) pathways. It is important in processes such as mood and stress response, the 5-HT pathway begins with the conversion of L-Trp to 5-hydroxytryptophan (5-HTP), that is metabolized into 5-HT, converted to melatonin or to 5-hydroxyindoleacetic acid (5-HIAA). Disturbances in this pathway are reported to be connected with oxidative stress and glucocorticoid-induced stress, are important to explore. Thus, our study aimed to understand the role of hydrogen peroxide (H2O2) and corticosterone (CORT)-induced stress on the serotonergic pathway of L-Trp metabolism, and on SH-SY5Y cells, focusing on the study of L-Trp, 5-HTP, 5-HT, and 5-HIAA in combination with H2O2 or CORT. We evaluated the effect of these combinations on cellular viability, morphology, and on the extracellular levels of the metabolites. The data obtained highlighted the different ways that stress induction led to different extracellular medium concentration of the studied metabolites. These distinct chemical transformations did not lead to differences in cell morphology/viability. Additionally, serotonin may be the most sensitive metabolite to the exposure to the different stress inducers, being more promissory to study conditions associated with cellular stress.

Keywords: 5-hydroxyindoleacetic acid; 5-hydroxytryptophan; glucocorticoids; oxidative stress; serotonin; tryptophan.

MeSH terms

  • 5-Hydroxytryptophan
  • Corticosterone
  • Humans
  • Hydrogen Peroxide
  • Hydroxyindoleacetic Acid / metabolism
  • Neuroblastoma*
  • Serotonin / metabolism
  • Tryptophan* / metabolism

Substances

  • Tryptophan
  • 5-Hydroxytryptophan
  • Serotonin
  • Hydrogen Peroxide
  • Corticosterone
  • Hydroxyindoleacetic Acid

Grants and funding

This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional— through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020—and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia—in a framework of the projects in CINTESIS, R and D Unit (reference UIDB/4255/2020), and within the scope of the project “RISE–LA/P/0053/2020. Nuno Vale thanks support from FCT and FEDER (European Union), award number IF/00092/2014/CP1255/CT0004 and CHAIR in Onco-Innovation at FMUP.