L-carnitine prevents ammonia-induced cytotoxicity and disturbances in intracellular amino acid levels in human astrocytes
L-carnitine prevents ammonia-induced cytotoxicity and disturbances in intracellular amino acid levels in human astrocytes
复制标题
左旋肉碱可防止氨诱导的细胞毒性和人星形胶质细胞内氨基酸水平的紊乱
DOI：
10.1111/jgh.14497
复制
发表时间：
2018
影响因子：
4.1
通讯作者：
Takikawa Yasuhiro
中科院分区：
文献类型：
--
作者：
Wang Ting;Suzuki Kazuyuki;Kakisaka Keisuke;Onodera Mio;Sawara Kei;Takikawa Yasuhiro
背景和目的左旋卡尼汀（L-CA）已被用于治疗肝性脑病伴高血氨症，但L-CA促进脑内氨解毒的机制尚不清楚。因此，细胞毒性和细胞内氨基酸（AAs）在星形胶质细胞与高氨血症后L-CA administration.MethodsHuman星形胶质细胞的变化进行了研究氯化铵（NH 4Cl），L-CA或NH 4Cl的混合物，和L-CA在规定的条件下。在不同的治疗阶段后，测定细胞内总活性氧和乳酸脱氢酶漏出。AAs在星形胶质细胞的细胞内水平测定使用代谢组学analysis.ResultsIntracellular总活性氧和乳酸脱氢酶泄漏显着增加与氯化铵治疗后。相比之下，与L-CA的共处理显著抑制NH 4Cl的细胞毒性作用。与对照细胞相比，NH 4Cl处理的细胞中几乎所有涉及谷氨酰胺和支链氨基酸（BCAA）的AA的细胞内水平均显著增加; L-CA共处理降低了BCAA水平的这些变化。此外，水平的3-甲基-2-氧代戊酸，这是从异亮氨酸的代谢产物，并在神经损伤中起着至关重要的作用，显着增加，在NH 4Cl处理的细胞，但这种代谢产物显着降低与L-CA co-treatment. ConclusionL-CA保护人星形胶质细胞从氨诱导的急性细胞毒性作用和谷氨酰胺和支链氨基酸的细胞内水平的增加。
Background and AimL‐carnitine (L‐CA) has been used therapeutically to treat hepatic encephalopathy with hyperammonemia, but the mechanism by which L‐CA contributes to ammonia detoxification in the brain is still unclear. Thus, the cytotoxicity and changes in intracellular amino acids (AAs) in astrocytes with hyperammonemia following L‐CA administration were studied.MethodsHuman astrocytes were treated with ammonium chloride (NH4Cl), L‐CA or a mixture of NH4Cl, and L‐CA under defined conditions. Total intracellular reactive oxygen species and lactate dehydrogenase leakage were measured following different treatment periods. The intracellular levels of AAs in astrocytes were determined using metabolomic analysis.ResultsIntracellular total reactive oxygen species and lactate dehydrogenase leakage were significantly increased after treatment with NH4Cl. In contrast, co‐treatment with L‐CA significantly inhibited the cytotoxic effects of NH4Cl. The intracellular levels of almost all AAs involving glutamine and branched‐chain AAs (BCAAs) were significantly increased in the NH4Cl‐treated cells compared with in the control cells; these changes in BCAA levels were reduced with L‐CA co‐treatment. Additionally, the level of 3‐methyl‐2‐oxovaleric acid, which is a metabolite from isoleucine and plays a critical role in neurological damage, was significantly increased in the NH4Cl‐treated cells, but this metabolite was significantly decreased with L‐CA co‐treatment.ConclusionL‐CA protects human astrocytes from ammonia‐induced acute cytotoxic effects and the increased intracellular levels of glutamine and BCAAs.