Gyawali Asmita, Hyeon Seung Jae, Ryu Hoon, Kang Young-Sook
College of Pharmacy and Drug Information Research Institute, Sookmyung Women's University, Seoul 04310, Korea.
Laboratory for Brain Gene Regulation and Epigenetics, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Korea.
Pharmaceutics. 2021 Apr 14;13(4):551. doi: 10.3390/pharmaceutics13040551.
L-Carnitine (LC) is essential for transporting fatty acids to the mitochondria for β-oxidation. This study was performed to examine the alteration of the LC transport system in wild type (WT, NSC-34/hSOD1) and mutant type (MT, NSC-34/hSOD1) amyotrophic lateral sclerosis (ALS) models. The uptake of [H]L-carnitine was dependent on time, temperature, concentration, sodium, pH, and energy in both cell lines. The Michaelis-Menten constant (K) value as well as maximum transport velocity (V) indicated that the MT cell lines showed the higher affinity and lower capacity transport system, compared to that of the WT cell lines. Additionally, LC uptake was inhibited by organic cationic compounds but unaffected by organic anions. OCTN1/slc22a4 and OCTN2/slc22a5 siRNA transfection study revealed both transporters are involved in LC transport in NSC-34 cell lines. Additionally, slc22a4 and slc22a5 was significantly decreased in mouse MT models compared with that in ALS WT littermate models in the immune-reactivity study. [H]L-Carnitine uptake and mRNA expression pattern showed the pretreatment of LC and acetyl L-carnitine (ALC) attenuated glutamate induced neurotoxicity in NSC-34 cell lines. These findings indicate that LC and ALC supplementation can prevent the neurotoxicity and neuro-inflammation induced by glutamate in motor neurons.
左旋肉碱（LC）对于将脂肪酸转运至线粒体进行β氧化至关重要。本研究旨在检测野生型（WT，NSC - 34/hSOD1）和突变型（MT，NSC - 34/hSOD1）肌萎缩侧索硬化症（ALS）模型中LC转运系统的变化。在两种细胞系中，[H]左旋肉碱的摄取均依赖于时间、温度、浓度、钠、pH值和能量。米氏常数（K）值以及最大转运速度（V）表明，与WT细胞系相比，MT细胞系表现出更高的亲和力和更低的转运能力。此外，LC摄取受到有机阳离子化合物的抑制，但不受有机阴离子的影响。OCTN1/slc22a4和OCTN2/slc22a5 siRNA转染研究表明，这两种转运体均参与NSC - 34细胞系中的LC转运。此外，在免疫反应性研究中，与ALS野生型同窝小鼠模型相比，小鼠MT模型中的slc22a4和slc22a5显著降低。[H]左旋肉碱摄取和mRNA表达模式表明，LC和乙酰左旋肉碱（ALC）预处理可减轻NSC - 34细胞系中谷氨酸诱导的神经毒性。这些发现表明，补充LC和ALC可预防谷氨酸在运动神经元中诱导的神经毒性和神经炎症。
