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用人类神经母细胞瘤细胞系(SH-SY5Y)研究过氧化氢和皮质酮应激对色氨酸代谢的影响。

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

机构信息

OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.

Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.

出版信息

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 (HO) 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 HO 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.

摘要

色氨酸(L-Trp)是几种生理机制中的重要氨基酸,其代谢分为两条重要途径:犬尿酸途径和血清素(5-HT)途径。它在情绪和应激反应等过程中很重要,5-HT 途径始于 L-Trp 转化为 5-羟色氨酸(5-HTP),然后转化为 5-HT,转化为褪黑素或 5-羟吲哚乙酸(5-HIAA)。据报道,该途径的紊乱与氧化应激和皮质酮诱导的应激有关,值得深入研究。因此,我们的研究旨在了解过氧化氢(HO)和皮质酮(CORT)诱导的应激对 L-Trp 代谢的 5-羟色氨酸途径的影响,并以 SH-SY5Y 细胞为研究对象,重点研究 L-Trp、5-HTP、5-HT 和 5-HIAA 与 HO 或 CORT 的结合。我们评估了这些组合对细胞活力、形态和代谢物细胞外水平的影响。所得数据突出了应激诱导以不同方式导致研究代谢物细胞外介质浓度不同。这些不同的化学转化并没有导致细胞形态/活力的差异。此外,血清素可能是对不同应激诱导剂暴露最敏感的代谢物,更适合研究与细胞应激相关的条件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13eb/10001894/ee7f3ac6021d/ijms-24-04389-g001.jpg

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