Pyruvate dehydrogenase complex and lactate dehydrogenase are targets for therapy of acute liver failure.

ABSTRACT:

Background & aims

Acute liver failure is a rapidly progressive deterioration of hepatic function resulting in high mortality and morbidity. Metabolic enzymes can translocate to the nucleus to regulate histone acetylation and gene expression.

Methods

Levels and activities of pyruvate dehydrogenase complex (PDHC) and lactate dehydrogenase (LDH) were evaluated in nuclear fractions of livers of mice exposed to various hepatotoxins including CD95-antibody, α-amanitin, and acetaminophen. Whole-genome gene expression profiling by RNA-seq was performed in livers of mice with acute liver failure and analyzed by gene ontology enrichment analysis. Cell viability was evaluated in cell lines knocked-down for PDHA1 or LDH-A and in cells incubated with the LDH inhibitor galloflavin after t

SUBMITTER: Ferriero R 

PROVIDER: S-EPMC6057136 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature