Transcriptomics

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The Autonomous Hepatocyte Clock Controls Acetaminophen Bioactivation and Chronotoxicity [Liver]


ABSTRACT: The diurnal variation in acetaminophen (APAP) hepatotoxicity (“chronotoxicity”) is thought to be due to oscillations in xenobiotic metabolism that are influenced by the circadian phases of feeding or fasting. Because of APAP’s relevance to human poisoning, we set out to determine the relative contributions of the central clock in the SCN and the autonomous clock in the hepatocyte in modulating the chronotoxicity of APAP. Using a conditional null allele of Mop3 (ArntL, Bmal1) we are able to delete the clock from hepatocytes while keeping the central and other peripheral clocks intact (eg, those controlling food intake). Our data from this hepatocyte-null mouse model suggests that, while the central circadian clock modulates some detoxification pathways indirectly by driving activity patterns and feeding rhythms, the autonomous hepatocyte circadian clock controls major aspects of APAP bioactivation independent of feeding rhythms.

ORGANISM(S): Mus musculus

PROVIDER: GSE34442 | GEO | 2013/08/30

SECONDARY ACCESSION(S): PRJNA156377

REPOSITORIES: GEO

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