Pretreatment Effect of Inflammatory Stimuli and Characteristics of Tryptophan Transport on Brain Capillary Endothelial (TR-BBB) and Motor Neuron Like (NSC-34) Cell Lines.

Asmita Gyawali,Young-Sook Kang

doi:10.3390/biomedicines9010009

Abstract

Tryptophan plays a key role in several neurological and psychiatric disorders. In this study, we investigated the transport mechanisms of tryptophan in brain capillary endothelial (TR-BBB) cell lines and motor neuron-like (NSC-34) cell lines. The uptake of [3H]l-tryptophan was stereospecific, and concentration- and sodium-dependent in TR-BBB cell lines. Transporter inhibitors and several neuroprotective drugs inhibited [3H]l-tryptophan uptake by TR-BBB cell lines. Gabapentin and baclofen exerted a competitive inhibitory effect on [3H]l-tryptophan uptake. Additionally, l-tryptophan uptake was time- and concentration-dependent in both NSC-34 wild type (WT) and mutant type (MT) cell lines, with a lower transporter affinity and higher capacity in MT than in WT cell lines. Gene knockdown of LAT1 (l-type amino acid transporter 1) and CAT1 (cationic amino acid transporter 1) demonstrated that LAT1 is primarily involved in the transport of [3H]l-tryptophan in both TR-BBB and NSC-34 cell lines. In addition, tryptophan uptake was increased by TR-BBB cell lines but decreased by NSC-34 cell lines after pro-inflammatory cytokine pre-treatment. However, treatment with neuroprotective drugs ameliorated tryptophan uptake by NSC-34 cell lines after inflammatory cytokines pretreatment. The tryptophan transport system may provide a therapeutic target for treating or preventing neurodegenerative diseases.

Highlights

Tryptophan, an essential amino acid for protein biosynthesis, is converted into bioactive metabolites such as serotonin, melatonin, and kynurenine to regulate several physiological processes [1,2]
kynurenine pathway (KP) byproduct such as quinolinic acid (an agonist of the N-methylD -aspartate (NMDA) receptor) cause neuronal dysfunction; an elevated level of quinolinic acid is indicative of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, autoimmune disease, psychiatric disease, epilepsy, and other infectious diseases [7,8]
These results indicated that L-tryptophan uptak. These results indicated that neutral amino acids (NAAs) significantly inhibited the upwastake time, and sodium-dependent, high-affinity and low-capacit of [3concentration, H]L-tryptophan, suggesting their involvementwith in theatransport of tryptophan in transport

Summary

Introduction

Tryptophan, an essential amino acid for protein biosynthesis, is converted into bioactive metabolites such as serotonin, melatonin, and kynurenine to regulate several physiological processes [1,2]. KP byproduct such as quinolinic acid (an agonist of the N-methylD -aspartate (NMDA) receptor) cause neuronal dysfunction; an elevated level of quinolinic acid is indicative of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, autoimmune disease, psychiatric disease, epilepsy, and other infectious diseases [7,8]. Another byproduct of this pathway is kynurenic acid, an NMDA antagonist, which helps prevent neuronal damage [6,9,10]

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