Transport Alteration of 4-Phenyl Butyric Acid Mediated by a Sodium- and Proton-Coupled Monocarboxylic Acid Transporter System in ALS Model Cell Lines (NSC-34) Under Inflammatory States

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

“…An excessive amount of TNF-α in neuronal cells can produce excessive extracellular glutamate levels and reduce glutamate clearance, whereas LPS treatment activates the production of intracellular molecules that further activate the production of inflammatory mediators, key factors in motor neuron damage, and diminishes the uptake of tryptophan in motor neurons [ 46 , 47 ]. Up- and down-regulation of transporters expression in the inflammatory state depended on the cell type; we observed similar results to those of a previous study with motor neuronal and endothelial cell lines [ 29 , 30 ]. Along with inflammatory stimuli, neuroprotective drugs such as baclofen, gabapentin, l -dopa, and verapamil restored tryptophan uptake by NSC-34 cell lines ( Figure 7 ).…”

“…Real-time PCR was performed in 48-well plates using the StepOne Real Time-PCR system (Applied Biosystems, Life Technologies) [ 24 , 27 ]. Similarly, LAT1 mRNA expression was assessed after 24-h pretreatment with LPS and TNF-α [ 30 ].…”

“…TR-BBB and NSC-34 cell lines were pre-treated with LPS (20 ng/mL) and TNF-α (20 ng/mL) for 24 h [ 29 , 30 , 31 ], followed by [ 3 H] l -tryptophan uptake analysis. Additionally, TNF-α/LPS-treated TR-BBB and NSC-34 cell lines were incubated for 24 h with LAT1 substrates/inhibitors or neuroprotective drugs, including baclofen (2 mM), gabapentin (0.5 mM), l -dopa (0.1 mM), and verapamil (0.1 mM), prior to [ 3 H] l -tryptophan uptake analysis.…”

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

“…The reduced uptake of L-lysine in MT cell lines might be due to mutation, deletion, or resistance of transporters, resulting in a lower transport activity as compared to that of the WT cell lines. Previous studies have reported similar results, as D-serine and PBA levels were decreased in MT cell lines of ALS ( Lee et al ., 2017 ; Gyawali and Kang, 2021b ). These results are in agreement with a previous report indicating that the level of L-lysine is increased in the lumbar spinal cord of a mutant SOD G93A model of ALS mice compared to that in WT mice ( Jung et al ., 2013 ).…”

“…K m1 is the Michaelis–Menten constant for the high-affinity process, and K m2 is the Michaelis–Menten constant for the low-affinity process. K ns1 and K ns2 are the first-order constants for the non-saturable components in the high-affinity and low-affinity processes, respectively ( Gyawali and Kang, 2021b ).…”