Supplementation with Branched-Chain Amino Acids Induces Unexpected Deleterious Effects on Astrocyte Survival and Intracellular Metabolism with or without Hyperammonemia: A Preliminary In Vitro Study

补充支链氨基酸会对伴有或不伴有高氨血症的星形胶质细胞存活和细胞内代谢产生意想不到的有害影响:一项初步体外研究

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作者:Ting Wang, Kazuyuki Suzuki, Toshimi Chiba, Keisuke Kakisaka, Yasuhiro Takikawa

Conclusions

Although further investigations of the effect of BCAA on human astrocytes with hyperammonemia are needed, our work demonstrates that BCAA supplementation has direct negative effects on astrocyte survival and intracellular metabolism.

Methods

We performed cytotoxicity and cell proliferation tests on astrocytes following BCAA treatment with and without ammonium chloride (NH4Cl) and then compared the

Results

The astrocytes showed increased leakage of intracellular lactate dehydrogenase and reduced proliferation rate upon BCAA treatment. Interestingly, our analysis showed a BCAA-induced impairment of intracellular glycolysis/glyconeogenesis as well as amino acid and butyric acid metabolism. Furthermore, BCAA treatment was found to cause decreased levels of Glut-1 and phosphorylated GSK-3β and mTOR in astrocytes. Conclusions: Although further investigations of the effect of BCAA on human astrocytes with hyperammonemia are needed, our work demonstrates that BCAA supplementation has direct negative effects on astrocyte survival and intracellular metabolism.

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