title: Perfluorodecanoic acid, a peroxisome proliferator, activates phospholipase C, inhibits CTP:phosphocholine cytidylyltransferase, and elevates diacylglycerol in rat liver.
abstract: Perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) are peroxisome proliferators that cause hepatotoxicity in rodents. This study shows that PFDA activates liver phospholipase C (PLC) and inhibits CTP:phosphocholine cytidylyltransferase (CT). PLC cytosolic and microsomal activities were increased 1.4- and 1.7-fold, respectively. CT activates were decreased to 58% (cytosol) and 36% (microsome) of control values. PFDA also caused a threefold increase in liver diacylglycerol (DAG) concentration. PFOA had no effect on the enzyme activities or DAG concentration. Together with previous results, these data suggest that PFDA activates a phosphatidylcholine-specific PLC causing an increase in liver phosphocholine and DAG. These effects are discussed in relation to cellular signalling processes that may provide a mechanism for PFDA-induced hepatotoxicity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Wright State University, Cox Institute, Dayton, Ohio 45429, USA.
authors.forename: N V
authors.initials: NV
authors.lastname: Reo
authors.forename: L
authors.initials: L
authors.lastname: Narayanan
authors.forename: K B
authors.initials: KB
authors.lastname: Kling
authors.forename: M
authors.initials: M
authors.lastname: Adinehzadeh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003600:Cytosol / Q000187:drug effects; D003652:Decanoic Acids / Q000633:toxicity*; D004075:Diglycerides / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D005466:Fluorocarbons / Q000633:toxicity*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000187:drug effects; D008861:Microsomes / Q000187:drug effects; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors* / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D010738:Type C Phospholipases / Q000187:drug effects* / Q000378:metabolism
chemical_list: D003652:Decanoic Acids; D004075:Diglycerides; D005466:Fluorocarbons; D010713:Phosphatidylcholines; C036567:perfluorodecanoic acid; D009713:Nucleotidyltransferases; D010738:Type C Phospholipases