Lipin deactivation after acetaminophen overdose causes phosphatidic acid accumulation in liver and plasma in mice and humans and enhances liver regeneration. (May 2018)

• Record Type: Journal Article
• Authors: Lutkewitte, Andrew J.; Schweitzer, George G.; Kennon-McGill, Stefanie; Clemens, Melissa M.; James, Laura P.; Jaeschke, Hartmut; Finck, Brian N.; McGill, Mitchell R.
• Is Part Of: Food and chemical toxicology. Volume 115(2018)
• Page Start: 273
• Page End: 283
• Publication Date: 2018-05
• Subjects: ALF acute liver failure -- ALT alanine aminotransferase -- APAP acetaminophen -- Gpat glycerol-3-phosphate acyltransferase -- LC-ESI-MS/MS liquid chromatography with electrospray ionization and tandem triple quadrupole mass spectrometry -- lyso-PA lysophosphatidic acid -- mTOR mechanistic target of rapamycin -- NAC N-acetylcysteine -- PA phosphatidic acid -- PAP phosphatidic acid phosphohydrolase -- PCNA proliferating cell nuclear antigen -- PHx partial hepatectomy -- ULN upper limit of normal; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.03.014
• Languages: English
• ISSNs: 0278-6915

Abstract

Highlights: Phosphatidic acid increases in liver and circulation in mice after APAP overdose. Phosphatidic acid increases in circulation of humans with APAP hepatotoxicity. Reducing phosphatidic acid content in the liver blunts liver regeneration. Phosphatidic acid may affect liver regeneration through mTOR signaling.