RNA-Sequencing of Transaldolase and Aldose Reducatase Deficiency in Mouse Liver
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ABSTRACT: Oxidative stress modulates carcinogenesis in the liver; however, direct evidence for metabolic control of oxidative stress during pathogenesis, particularly, of progression from cirrhosis to hepatocellular carcinoma (HCC), has been lacking. Deficiency of transaldolase (TAL), a ratelimiting enzyme of the non-oxidative branch of the pentose phosphate pathway (PPP), elicits growth restriction, and predisposes to cirrhosis and HCC in mice and humans. Here, we show that mitochondrial oxidative stress and disease progression from cirrhosis to HCC and acetaminophen-induced liver necrosis are critically dependent on NADPH depletion by aldose reductase (AR), while this enzyme protects from carbon trapping in the PPP and stunted growth in TAL deficiency. Both TAL and AR are confined to the cytosol, however, their inactivation distorts NADPH production and mitochondrial oxidative stress into opposite directions.
ORGANISM(S): Mus musculus
PROVIDER: GSE217133 | GEO | 2023/01/13
REPOSITORIES: GEO
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