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

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 [ H]l-tryptophan was stereospecific, and co...

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Bibliographic Details
Published in:Biomedicines 2020-12, Vol.9 (1), p.9
Main Authors: Gyawali, Asmita, Kang, Young-Sook
Format: Article
Language:English
Subjects:
Amino acids
Amyotrophic lateral sclerosis
Baclofen
Blood-brain barrier
By products
Cell lines
Cytokines
Disease prevention
Drug development
Free radicals
Gabapentin
Gene expression
Inflammation
l -type amino acid transporter 1 system
Mental disorders
Metabolites
motor neuron-like cell lines
Neurodegeneration
neurodegenerative disease
Neurodegenerative diseases
Neurological diseases
Neuroprotection
Oxidative stress
Serotonin
Tryptophan
Tumor necrosis factor-TNF
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Summary: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 [ H]l-tryptophan was stereospecific, and concentration- and sodium-dependent in TR-BBB cell lines. Transporter inhibitors and several neuroprotective drugs inhibited [ H]l-tryptophan uptake by TR-BBB cell lines. Gabapentin and baclofen exerted a competitive inhibitory effect on [ H]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 [ H]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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines9010009