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

Gyawali, Asmita; Kang, Young‐Sook

doi:10.3390/biomedicines9010009

Cited by 14 publications

(8 citation statements)

References 52 publications

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“…We hypothesize that the alteration in the expression of transporters in the presence of pro-inflammatory cytokines might be the reason for the reduction in the uptake of [ 3 H]L-lysine. As reported in a previous article, depending on the cell type, there is up- and down-regulation of transporter expression in the inflammatory state ( Gyawali and Kang, 2021a ). However, in the MT cell lines, co-treatment with L-lysine had a protective effect against pro-inflammatory cytokine states.…”

Section: Discussionsupporting

confidence: 59%

Change in Cationic Amino Acid Transport System and Effect of Lysine Pretreatment on Inflammatory State in Amyotrophic Lateral Sclerosis Cell Model

Latif

Kang

2021

Biomolecules & Therapeutics

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Amyotrophic lateral sclerosis (ALS) is a lethal neurological disorder characterized by the deterioration of motor neurons. The aim of this study was to investigate alteration of cationic amino acid transporter (CAT-1) activity in the transport of lysine and the pretreatment effect of lysine on pro-inflammatory states in an amyotrophic lateral sclerosis cell line. The mRNA expression of cationic amino acid transporter 1 was lower in NSC-34/hSOD1 G93A (MT) than the control cell line (WT), lysine transport is mediated by CAT-1 in NSC-34 cell lines. The uptake of [ 3 H]L-lysine was Na + -independent, voltage-sensitive, and strongly inhibited by inhibitors and substrates of cationic amino acid transporter 1 (system y + ). The transport process involved two saturable processes in both cell lines. In the MT cell line, at a high-affinity site, the affinity was 9.4-fold higher and capacity 24-fold lower than that in the WT; at a low-affinity site, the capacity was 2.3-fold lower than that in the WT cell line. Donepezil and verapamil competitively inhibited [ 3 H]L-lysine uptake in the NSC-34 cell lines. Pretreatment with pro-inflammatory cytokines decreased the uptake of [ 3 H]L-lysine and mRNA expression levels in both cell lines; however, the addition of L-lysine restored the transport activity in the MT cell lines. L-Lysine exhibited neuroprotective effects against pro-inflammatory states in the ALS disease model cell lines. In conclusion, studying the alteration in the expression of transporters and characteristics of lysine transport in ALS can lead to the development of new therapies for neurodegenerative diseases.

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Section: Discussionsupporting

confidence: 59%

Change in Cationic Amino Acid Transport System and Effect of Lysine Pretreatment on Inflammatory State in Amyotrophic Lateral Sclerosis Cell Model

Latif

Kang

2021

Biomolecules & Therapeutics

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“…Other glucose transporters are also modulated, as another report has shown that LPS endotoxin enhanced GLUT3 [119]. Moreover, amino-acid transport at the BBB level suffers alteration in inflammatory states, as shown in a recent paper assessing the increase in tryptophan uptake by the transport mechanisms of tryptophan in brain capillary endothelial as an effect of neuroinflammation (LPS and TNF-α as main triggers) [120]. Another in vivo study [94] demonstrated the downregulation of L-type amino acid transporter 1 (LAT1) in inflammatory states, with the thyroid hormone passage being modulated similarly to other important biomolecules (adenosine, insulin) in neuroinflammation.…”

Section: 11 Alteration Of Ecs During Inflammationmentioning

confidence: 93%

The Blood–Brain Barrier—A Key Player in Multiple Sclerosis Disease Mechanisms

2022

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Over the past decade, multiple sclerosis (MS), a chronic neuroinflammatory disease with severe personal and social consequences, has undergone a steady increase in incidence and prevalence rates worldwide. Despite ongoing research and the development of several novel therapies, MS pathology remains incompletely understood, and the prospect for a curative treatment continues to be unpromising in the near future. A sustained research effort, however, should contribute to a deeper understanding of underlying disease mechanisms, which will undoubtedly yield improved results in drug development. In recent years, the blood–brain barrier (BBB) has increasingly become the focus of many studies as it appears to be involved in both MS disease onset and progression. More specifically, neurovascular unit damage is believed to be involved in the critical process of CNS immune cell penetration, which subsequently favors the development of a CNS-specific immune response, leading to the classical pathological and clinical hallmarks of MS. The aim of the current narrative review is to merge the relevant evidence on the role of the BBB in MS pathology in a comprehensive and succinct manner. Firstly, the physiological structure and functions of the BBB as a component of the more complex neurovascular unit are presented. Subsequently, the authors review the specific alteration of the BBB encountered in different stages of MS, focusing on both the modifications of BBB cells in neuroinflammation and the CNS penetration of immune cells. Finally, the currently accepted theories on neurodegeneration in MS are summarized.

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“…ALS is linked to pathological features such as protein misfolding, impaired axonal transport, glutamate excitotoxicity, oxidative stress, endoplasmic reticulum (ER) stress, neuroinflammation, and mitochondrial dysfunction [3]. In SOD1 mutant models, essential transporters such as monocarboxylate transporters (MCTs), large neutral amino acid transporter 1 (LAT1), and organic cation/carnitine transporters 1 and 2 (OCTN1 and 2), are reportedly altered [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Monocarboxylate transporter functions and neuroprotective effects of valproic acid in experimental models of amyotrophic lateral sclerosis

et al. 2022

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Background Amyotrophic lateral sclerosis (ALS) is a devasting neurodegenerative disorder for which no successful therapeutics are available. Valproic acid (VPA), a monocarboxylate derivative, is a known antiepileptic drug and a histone deacetylase inhibitor. Methods To investigate whether monocarboxylate transporter 1 (MCT1) and sodium-coupled MCT1 (SMCT1) are altered in ALS cell and mouse models, a cellular uptake study, quantitative real time polymerase chain reaction and western blot parameters were used. Similarly, whether VPA provides a neuroprotective effect in the wild-type (WT; hSOD1WT) and ALS mutant-type (MT; hSOD1G93A) NSC-34 motor neuron-like cell lines was determined through the cell viability assay. Results [3H]VPA uptake was dependent on time, pH, sodium and concentration, and the uptake rate was significantly lower in the MT cell line than the WT cell line. Interestingly, two VPA transport systems were expressed, and the VPA uptake was modulated by SMCT substrates/inhibitors in both cell lines. Furthermore, MCT1 and SMCT1 expression was significantly lower in motor neurons of ALS (G93A) model mice than in those of WT mice. Notably, VPA ameliorated glutamate- and hydrogen peroxide-induced neurotoxicity in both the WT and MT ALS cell lines. Conclusions Together, the current findings demonstrate that VPA exhibits a neuroprotective effect regardless of the dysfunction of an MCT in ALS, which could help develop useful therapeutic strategies for ALS.

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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

Cited by 14 publications

References 52 publications

Change in Cationic Amino Acid Transport System and Effect of Lysine Pretreatment on Inflammatory State in Amyotrophic Lateral Sclerosis Cell Model

Change in Cationic Amino Acid Transport System and Effect of Lysine Pretreatment on Inflammatory State in Amyotrophic Lateral Sclerosis Cell Model

The Blood–Brain Barrier—A Key Player in Multiple Sclerosis Disease Mechanisms

Monocarboxylate transporter functions and neuroprotective effects of valproic acid in experimental models of amyotrophic lateral sclerosis

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