Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner.

ABSTRACT: Astrocyte dysfunction is a primary factor in hepatic encephalopathy (HE) impairing neuronal activity under hyperammonemia. In particular, the early events causing ammonia-induced toxicity to astrocytes are not well understood. Using established cellular HE models, we show that mitochondria rapidly undergo fragmentation in a reversible manner upon hyperammonemia. Further, in our analyses, within a timescale of minutes, mitochondrial respiration and glycolysis were hampered, which occurred in a pH-independent manner. Using metabolomics, an accumulation of glucose and numerous amino acids, including branched chain amino acids, was observed. Metabolomic tracking of ¹⁵N-labeled ammonia showed rapid incorporation of ¹⁵N into glutamate and glutamate-derived amino acids. Down

SUBMITTER: Drews L 

PROVIDER: S-EPMC7657470 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature