title: Protective effect of the Y220C mutant p53 against steatosis: good news?
abstract: Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to steatohepatitis, which may progress to fibrosis, and cirrhosis, leading eventually to hepatocarcinoma development. Recently, cases of hepatocarcinoma have been diagnosed in steatotic patients without nonalcoholic steatohepatitis (NASH) and cirrhosis. The p53 protein, besides its function as tumor suppressor, is emerging as an important regulator of cellular metabolism, but its role in steatosis remains unclear. We induced steatosis in HepG2 (wt-p53) and Huh7.5.1 (Y220C-mutant p53) cells using free fatty acids. We observed a different modulation of p53, different intracellular lipid content, and similar down-regulation of the de novo lipid synthesis genes but opposite modulation of the fatty acid β-oxidation pathway between HepG2 and Huh7.5.1. Accordingly, we found a diverse amount of apoptosis and reactive oxygen species between the two cell lines. Transfection of the wt-p53 in Huh7.5.1 cells reverted the different lipid metabolism behavior observed in these cells. In conclusion, unlike the wt-p53, the Y220C mutant provides a specific protection against steatosis and potentially against its progression. Our findings highlight for the first time an unknown role of a p53 mutant in the setting of steatosis. Being this mutation very frequent in human cancers, this study could be a breakthrough in explaining the occurrence of hepatocarcinoma in steatotic patients without NASH and cirrhosis.
authors.affiliation: Laboratory of Molecular Virology and Oncology, Francesco Balsano Foundation, Rome, Italy.
authors.forename: Manuele
authors.initials: M
authors.lastname: Gori
authors.forename: Barbara
authors.initials: B
authors.lastname: Barbaro
authors.forename: Mario
authors.initials: M
authors.lastname: Arciello
authors.forename: Roberta
authors.initials: R
authors.lastname: Maggio
authors.forename: Carmela
authors.initials: C
authors.lastname: Viscomi
authors.forename: Alessia
authors.initials: A
authors.lastname: Longo
authors.forename: Clara
authors.initials: C
authors.lastname: Balsano
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53