The Alteration of L-Carnitine Transport and Pretreatment Effect under Glutamate Cytotoxicity on Motor Neuron-Like NSC-34 Lines
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<sup>WT</sup>) and mutant type (MT, NSC-34/hSOD1<sup>G93A</sup>) amyotro...
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| Online Access: | https://www.mdpi.com/1999-4923/13/4/551 |
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| author | Asmita Gyawali Seung Jae Hyeon Hoon Ryu Young-Sook Kang |
| author_facet | Asmita Gyawali Seung Jae Hyeon Hoon Ryu Young-Sook Kang |
| author_sort | Asmita Gyawali |
| collection | DOAJ |
| description | 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<sup>WT</sup>) and mutant type (MT, NSC-34/hSOD1<sup>G93A</sup>) amyotrophic lateral sclerosis (ALS) models. The uptake of [<sup>3</sup>H]L-carnitine was dependent on time, temperature, concentration, sodium, pH, and energy in both cell lines. The Michaelis–Menten constant (K<sub>m</sub>) value as well as maximum transport velocity (V<sub>max</sub>) 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. [<sup>3</sup>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. |
| first_indexed | 2024-03-10T12:19:17Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T12:19:17Z |
| publishDate | 2021-04-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-2efa6cea00354dc0b92618a09f792b362023-11-21T15:35:02ZengMDPI AGPharmaceutics1999-49232021-04-0113455110.3390/pharmaceutics13040551The Alteration of L-Carnitine Transport and Pretreatment Effect under Glutamate Cytotoxicity on Motor Neuron-Like NSC-34 LinesAsmita Gyawali0Seung Jae Hyeon1Hoon Ryu2Young-Sook Kang3College of Pharmacy and Drug Information Research Institute, Sookmyung Women’s University, Seoul 04310, KoreaLaboratory for Brain Gene Regulation and Epigenetics, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, KoreaLaboratory for Brain Gene Regulation and Epigenetics, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, KoreaCollege of Pharmacy and Drug Information Research Institute, Sookmyung Women’s University, Seoul 04310, KoreaL-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<sup>WT</sup>) and mutant type (MT, NSC-34/hSOD1<sup>G93A</sup>) amyotrophic lateral sclerosis (ALS) models. The uptake of [<sup>3</sup>H]L-carnitine was dependent on time, temperature, concentration, sodium, pH, and energy in both cell lines. The Michaelis–Menten constant (K<sub>m</sub>) value as well as maximum transport velocity (V<sub>max</sub>) 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. [<sup>3</sup>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.https://www.mdpi.com/1999-4923/13/4/551L-carnitineuptake studyOCTN1 and 2NSC-34 cell linesamyotrophic lateral sclerosisglutamate neurotoxicity |
| spellingShingle | Asmita Gyawali Seung Jae Hyeon Hoon Ryu Young-Sook Kang The Alteration of L-Carnitine Transport and Pretreatment Effect under Glutamate Cytotoxicity on Motor Neuron-Like NSC-34 Lines Pharmaceutics L-carnitine uptake study OCTN1 and 2 NSC-34 cell lines amyotrophic lateral sclerosis glutamate neurotoxicity |
| title | The Alteration of L-Carnitine Transport and Pretreatment Effect under Glutamate Cytotoxicity on Motor Neuron-Like NSC-34 Lines |
| title_full | The Alteration of L-Carnitine Transport and Pretreatment Effect under Glutamate Cytotoxicity on Motor Neuron-Like NSC-34 Lines |
| title_fullStr | The Alteration of L-Carnitine Transport and Pretreatment Effect under Glutamate Cytotoxicity on Motor Neuron-Like NSC-34 Lines |
| title_full_unstemmed | The Alteration of L-Carnitine Transport and Pretreatment Effect under Glutamate Cytotoxicity on Motor Neuron-Like NSC-34 Lines |
| title_short | The Alteration of L-Carnitine Transport and Pretreatment Effect under Glutamate Cytotoxicity on Motor Neuron-Like NSC-34 Lines |
| title_sort | alteration of l carnitine transport and pretreatment effect under glutamate cytotoxicity on motor neuron like nsc 34 lines |
| topic | L-carnitine uptake study OCTN1 and 2 NSC-34 cell lines amyotrophic lateral sclerosis glutamate neurotoxicity |
| url | https://www.mdpi.com/1999-4923/13/4/551 |
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