title: Aflatoxin B1 misregulates the activity of serine proteases: possible implications in the toxicity of some mycotoxin.
abstract: Aflatoxins are highly hazardous contaminants of common food and feed. Aflatoxin B1 in particular, the most predominant among aflatoxins, was thoroughly demonstrated to be highly toxic, mutagenic, teratogenic and carcinogenic in many animal species. Besides its established targets and effects, this work investigates on the possible direct interaction between aflatoxin B1 and three major serine proteases, namely elastase, thrombin and trypsin. These proteases belongs to a class of structurally and functionally related proteins pivotal in both direct and indirect regulation of a number of cellular events. Additionally, several pathological processes, including cancer, inflammatory processes and thrombosis, rely upon the subtle equilibrium between these enzymes and their potential modulators: in fact, their misregulation, caused by foreign molecules, could facilitate (or be the cause for) the occurrence of these pathologies. Our results provide the evidence for a reversible binding between AFB1 and these enzymes, likely to have profound implications in the manifestation of aflatoxicosis. Precisely, the toxin behaved as a moderate competitive inhibitor toward the enzymatic activity of the serine proteases in the low micromolar range.
authors.affiliation: University of Camerino, MCAB Department, Via Gentile III da Varano, 62032 Camerino, Italy. massimiliano.cuccioloni@unicam.it
authors.forename: M
authors.initials: M
authors.lastname: Cuccioloni
authors.forename: M
authors.initials: M
authors.lastname: Mozzicafreddo
authors.forename: S
authors.initials: S
authors.lastname: Barocci
authors.forename: F
authors.initials: F
authors.lastname: Ciuti
authors.forename: L
authors.initials: L
authors.lastname: Re
authors.forename: A M
authors.initials: AM
authors.lastname: Eleuteri
authors.forename: M
authors.initials: M
authors.lastname: Angeletti
mesh_terms: D016604:Aflatoxin B1 / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002417:Cattle; D006801:Humans; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D010599:Pharmacokinetics; D011042:Poisons / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D011485:Protein Binding; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D014357:Trypsin / Q000737:chemistry / Q000378:metabolism
chemical_list: D011042:Poisons; D015842:Serine Proteinase Inhibitors; D016604:Aflatoxin B1; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D014357:Trypsin; D013917:Thrombin