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

Authors
Gyawali, AsmitaKang, Young-Sook
Issue Date
Jan-2021
Publisher
MDPI
Keywords
tryptophan; blood-brain barrier; l-type amino acid transporter 1 system; amyotrophic lateral sclerosis; neurodegenerative disease; motor neuron-like cell lines
Citation
BIOMEDICINES, v.9, no.1, pp 1 - 15
Pages
15
Journal Title
BIOMEDICINES
Volume
9
Number
1
Start Page
1
End Page
15
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/146192
DOI
10.3390/biomedicines9010009
ISSN
2227-9059
2227-9059
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 [H-3]l-tryptophan was stereospecific, and concentration- and sodium-dependent in TR-BBB cell lines. Transporter inhibitors and several neuroprotective drugs inhibited [H-3]l-tryptophan uptake by TR-BBB cell lines. Gabapentin and baclofen exerted a competitive inhibitory effect on [H-3]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-3]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.
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