title: Down-regulation of LPCAT expression increases platelet-activating factor level in cirrhotic rat liver: potential antiinflammatory effect of silybin.
abstract: Cholestasis is one of the major causes of liver diseases. A chronic accumulation of toxic bile acids in the liver, which occurs in this condition, can induce fibrosis and cirrhosis. Inflammation is a fundamental component of acute and chronic cholestatic liver injury. Platelet-activating factor (PAF) is a proinflammatory lipid which may be generated by two independent pathways called the de novo and remodeling pathway being the last responsible for the synthesis of PAF during inflammation. In recent years a key role in PAF remodeling has been attributed to lysophosphatidylcholine acyltransferase (LPCAT) enzymes. Although the knowledge on their characteristic is growing, the exact mechanism of LPCAT in pathological conditions remains still unknown. Here, we reported that the level of lyso-PAF and PAF significantly increased in the liver of cirrhotic vs. control rats together with a significant decrease in both mRNA abundance and protein level of both LPCAT1 and LPCAT2. Acyltransferase activities of both LPCAT1 and LPCAT2 were parallel decreased in the liver of cirrhotic animals. Interestingly, treatment with silybin strongly decreased the level of both pro-inflammatory lipids and restored the activity and expression of both LPCAT1 and LPCAT2 of cirrhotic liver. Silybin effect was specific for LPCAT1 and LPCAT2 since it did not affect LPCAT3 mRNA abundance of cirrhotic liver.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Stanca
authors.forename: Gaetano
authors.initials: G
authors.lastname: Serviddio
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellanti
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Vendemiale
authors.forename: Luisa
authors.initials: L
authors.lastname: Siculella
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Giudetti
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002855:Chromatography, Thin Layer; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008103:Liver Cirrhosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism; D010972:Platelet Activating Factor / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D012838:Silymarin; D000077385:Silybin; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D054467:Phospholipases A2
keywords: Biliary cirrhosis; Lysophosphatidylcholine acyltransferase; Platelet-activating factor; Silybin