Paraoxonases (PON1, PON2, PON3) analyses in vitro and in vivo in relation to cardiovascular diseases.
Mammalian paraoxonases (PON1, PON2, PON3) are a unique family of calcium-dependent hydrolases, with enzymatic activities toward a broad range of substrates (lactones, thiolactones, carbonates, esters, phosphotriesters). Although PONs physiological substrates were not yet identified, some studies suggest that they could be some lactones, or some specific oxidized phospholipids, or products of both enzymatic and nonenzymatic oxidation of arachidonic and docosahexaenoic acid, as well as N-acyl-homoserine lactones (which are quorum-sensing signals of pathogenic bacteria). Since no endogenous substrates for PONs activity determination are available yet, synthetic substrates such as paraoxon, phenyl acetate, and several lactones are used for PONs activity assays. All three members of the PON family (PON 1/2/3) were shown to protect from atherosclerosis development. Their anti-atherogenic biological activities were studied in vitro using serum or cell cultures, and also in vivo, using PON 1/2/3 knockout or transgenic mice, as well as humans - healthy volunteers and atherosclerotic patients (diabetics, hypercholesterolemics, and hypertensives).
Aviram
Michael
M
Lipid Research Laboratory, Technion Faculty of Medicine and Department of Laboratory Medicine, Rambam Medical Center, Haifa, Israel.
Rosenblat
Mira
M
D000818:Animals; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000235:genetics / Q000302:isolation & purification; D001671:Biochemistry / Q000379:methods*; D015153:Blotting, Western; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000201:enzymology*; D002460:Cell Line; D004789:Enzyme Activation; D004795:Enzyme Stability; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008075:Lipoproteins, HDL; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D002265:Carboxylic Ester Hydrolases; D043303:Aryldialkylphosphatase