Perfluorodecanoic acid, a peroxisome proliferator, activates phospholipase C, inhibits CTP:phosphocholine cytidylyltransferase, and elevates diacylglycerol in rat liver.
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.
Reo
N V
NV
Department of Biochemistry and Molecular Biology, Wright State University, Cox Institute, Dayton, Ohio 45429, USA.
Narayanan
L
L
Kling
K B
KB
Adinehzadeh
M
M
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
D003652:Decanoic Acids; D004075:Diglycerides; D005466:Fluorocarbons; D010713:Phosphatidylcholines; C036567:perfluorodecanoic acid; D009713:Nucleotidyltransferases; D010738:Type C Phospholipases