Investigations Towards Tryptophan Uptake and Transport Across an In Vitro Model of the Oral Mucosa Epithelium.

IF 2.7 Q3 NEUROSCIENCES
International Journal of Tryptophan Research Pub Date : 2024-07-31 eCollection Date: 2024-01-01 DOI:10.1177/11786469241266312
Grace C Lin, Julia Tevini, Lisa Mair, Heinz-Peter Friedl, Dietmar Fuchs, Thomas Felder, Johanna M Gostner, Winfried Neuhaus
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Abstract

Tryptophan is an essential amino acid and plays an important role in several metabolic processes relevant for the human health. As the main metabolic pathway for tryptophan along the kynurenine axis is involved in inflammatory responses, changed metabolite levels can be used to monitor inflammatory diseases such as ulcerative colitis. As a progenitor of serotonin, altered tryptophan levels have been related to several neurogenerative diseases as well as depression or anxiety. While tryptophan concentrations are commonly evaluated in serum, a non-invasive detection approach using saliva might offer significant advantages, especially during long-term treatments of patients or elderly. In order to estimate whether active transport processes for tryptophan might contribute to a potential correlation between blood and saliva tryptophan concentrations, we investigated tryptophan's transport across an established oral mucosa in vitro model. Interestingly, treatment with tryptophan revealed a concentration dependent secretion of tryptophan and the presence of a saturable transporter while transport studies with deuterated tryptophan displayed increased permeability from the saliva to the blood compartment. Protein analysis demonstrated a distinct expression of L-type amino acid transporter 1 (LAT1), the major transporter for tryptophan, and exposure to inhibitors (2 -amino-2-norbornanecarboxylic acid (BCH), L-leucine) led to increased tryptophan levels on the saliva side. Additionally, exposure to tryptophan in equilibrium studies resulted in a regulation of LAT1 at the mRNA level. The data collected in this study suggest the participation of active transport mechanisms for tryptophan across the oral mucosa epithelium. Future studies should investigate the transport of tryptophan across salivary gland epithelia in order to enable a comprehensive understanding of tryptophan exchange at the blood-saliva barrier.

色氨酸在口腔黏膜上皮细胞体外模型中的吸收和转运研究
色氨酸是人体必需的氨基酸,在与人体健康相关的多个代谢过程中发挥着重要作用。由于色氨酸沿着犬尿氨酸轴的主要代谢途径涉及炎症反应,因此代谢物水平的变化可用于监测溃疡性结肠炎等炎症性疾病。作为血清素的祖先,色氨酸水平的改变与多种神经变性疾病以及抑郁或焦虑有关。虽然色氨酸浓度通常在血清中进行评估,但利用唾液进行无创检测的方法可能具有显著优势,尤其是在对患者或老年人进行长期治疗期间。为了估计色氨酸的主动转运过程是否会导致血液和唾液中色氨酸浓度之间的潜在相关性,我们研究了色氨酸在已建立的口腔粘膜体外模型中的转运过程。有趣的是,用色氨酸处理后发现色氨酸的分泌与浓度有关,并且存在可饱和的转运体,而用氚代色氨酸进行的转运研究显示,从唾液到血液的通透性增加了。蛋白质分析表明,色氨酸的主要转运体 L 型氨基酸转运体 1 (LAT1) 有明显的表达,而且接触抑制剂(2-氨基-2-降冰片烷羧酸 (BCH)、L-亮氨酸)会导致唾液中的色氨酸含量增加。此外,在平衡研究中接触色氨酸会在 mRNA 水平上调节 LAT1。本研究收集的数据表明,色氨酸在口腔黏膜上皮细胞中参与了主动转运机制。今后的研究应调查色氨酸在唾液腺上皮细胞中的转运情况,以便全面了解色氨酸在血液-唾液屏障中的交换情况。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.30
自引率
4.50%
发文量
19
审稿时长
8 weeks
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