Ataxia telangiectasia mutated pathway disruption affects hepatic DNA and tissue damage in nonalcoholic fatty liver disease.

ABSTRACT: To overcome the rising burdens of nonalcoholic fatty liver disease, mechanistic linkages in mitochondrial dysfunction, inflammation and hepatic injury are critical. As ataxia telangiectasia mutated (ATM) gene oversees DNA integrity and mitochondrial homeostasis, we analyzed mRNAs and total proteins or phosphoproteins related to ATM gene by arrays in subjects with healthy liver, fatty liver or nonalcoholic steatohepatitis. Functional genomics approaches were used to query DNA damage or cell growth events. The effects of fatty acid-induced toxicity in mitochondrial health, DNA integrity and cell proliferation were validated in HuH-7 cells, including by inhibiting ATM kinase activity or knckdown of its mRNA. In fatty livers, DNA damage and ATM pathway activation was observed. During induced s

SUBMITTER: Viswanathan P 

PROVIDER: S-EPMC7080576 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature