title: Diesel and biodiesels induce hepatic palmitoyl-CoA oxidase enzymatic activity through different molecular mechanisms in rats.
abstract: Induction of palmitoyl-CoA oxidase enzymatic activity in rat liver suggests that ingestion of diesel and biodiesels can cause mild hepatic peroxisomal proliferation. Surprisingly, quantification by immunochemistry of the enzyme itself (ACOX1) revealed that palmitoyl-CoA oxidase enzymatic activity correlates with ACOX1 protein level following exposure to diesel, but not following exposure to biodiesels. Quantification of CYP4A1, another biomarker of peroxisomal proliferation, further indicates that contrary to diesel, the effects of biodiesels appear to be independent of this pathway. There are two ACOX1 protein isoforms that exhibit different enzymatic activities depending on the substrate. The results of our enzymatic assays performed on substrates presenting different carbon chain lengths (octanoyl-CoA and palmitoyl-CoA) are compatible with the hypothesis of a differential regulation of the ACOX1 isoforms by diesel and biodiesels. Further studies will be required to precisely determine the molecular mechanisms by which diesel and biodiesels induce palmitoyl-CoA oxidase activity in rat liver.
authors.affiliation: Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0l2, Canada. guillaume_pelletier@hc-sc.gc.ca
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pelletier
authors.forename: Marc
authors.initials: M
authors.lastname: Rigden
authors.forename: Raymond
authors.initials: R
authors.lastname: Poon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004790:Enzyme Induction; D005742:Gasoline / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
chemical_list: D005742:Gasoline; D010088:Oxidoreductases; C028427:palmitoyl CoA oxidase