Gyawali Asmita, Kang Young-Sook
Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil 100 (Cheongpa-dong 2ga), Yongsan-gu, Seoul 04310, Korea.
Biomedicines. 2020 Dec 24;9(1):9. doi: 10.3390/biomedicines9010009.
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.
色氨酸在多种神经和精神疾病中起着关键作用。在本研究中，我们调查了色氨酸在脑微血管内皮（TR-BBB）细胞系和运动神经元样（NSC-34）细胞系中的转运机制。[H]l-色氨酸的摄取具有立体特异性，且在TR-BBB细胞系中具有浓度依赖性和钠依赖性。转运体抑制剂和几种神经保护药物可抑制TR-BBB细胞系对[H]l-色氨酸的摄取。加巴喷丁和巴氯芬对[H]l-色氨酸的摄取具有竞争性抑制作用。此外，l-色氨酸的摄取在NSC-34野生型（WT）和突变型（MT）细胞系中均具有时间和浓度依赖性，MT细胞系中的转运体亲和力较低但容量较高。LAT1（l型氨基酸转运体1）和CAT1（阳离子氨基酸转运体1）的基因敲除表明，LAT1主要参与TR-BBB和NSC-34细胞系中[H]l-色氨酸的转运。此外，促炎细胞因子预处理后，TR-BBB细胞系的色氨酸摄取增加，而NSC-34细胞系的色氨酸摄取减少。然而，神经保护药物治疗可改善炎症细胞因子预处理后NSC-34细胞系的色氨酸摄取。色氨酸转运系统可能为治疗或预防神经退行性疾病提供一个治疗靶点。
