title: Lysine Adduction by Reactive Metabolite(s) of Monocrotaline.
abstract: Pyrrolizidine alkaloids (PAs) are known hepatotoxins. The execution of the toxicities of the alkaloids requires metabolic activation. Protein modification by reactive metabolites of PAs has been suggested to be an important mechanism of the toxic actions of PAs. The objectives of the present study were to define the interactions of dehydromonocrotaline (DHM) with lysine, lysine derivatives, a model peptide, and bovine serum albumin and to explore the lysine modification of hepatic proteins of animals given monocrotaline. DHM was found to react with the ε-amino group of all model compounds tested after incubation with DHM, and the modification reaction preferentially occurred at C7 of the necine base. The lysine residue modification with the same regioselectivity was also observed in hepatic proteins of mice treated with monocrotaline. The observed modification increased with the increase in doses administered to the animals. This work allowed us to better understand the mechanisms of the hepatotoxicity of monocrotaline.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong , Shatin, NT, Hong Kong SAR, Hong Kong.
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, Division of Gastroenterology and Hepatology, Department of Pediatrics, University of Washington School of Medicine , Seattle, Washington 98102, United States.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002417:Cattle; D007274:Injections, Intraperitoneal; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016686:Monocrotaline / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism
chemical_list: D010455:Peptides; D012710:Serum Albumin, Bovine; D016686:Monocrotaline; D008239:Lysine