title: Quercetin modulates activities of Taiwan cobra phospholipase A2 via its effects on membrane structure and membrane-bound mode of phospholipase A2.
abstract: The goal of the present study is to elucidate the mechanism of quercetin on modulating Naja naja atra phospholipase A2 (PLA2) activities. Sphingomyelin inhibited PLA2 enzymatic activity and membrane-damaging activity against egg yolk phosphatidylcholine (EYPC), while cholesterol and quercetin abrogated the sphingomeyelin inhibitory effect. Quercetin incorporation led to a reduction in PLA2 enzymatic activity and membrane-damaging activity toward EYPC/sphingomyelin/cholesterol vesicles. Both cholesterol and quercetin increased detergent resistance and reduced membrane fluidity of EYPC/sphingomyelin vesicles. Quercetin reduced detergent insolubility but increased ordered lipid packing of EYPC/sphingomyelin/cholesterol vesicles. Acrylamide quenching studies and trinitrophenylation of Lys residues revealed that quercetin altered the membrane-bound mode of PLA2 differently upon absorption onto the membrane bilayers of different lipid compositions. However, 8-anilinonaphthalene sulphonate-binding assay revealed that quercetin marginally affected the interaction between active site of PLA2 with phospholipid vesicles. Collectively, our data indicate that membrane-inserted quercetin modulates PLA2 interfacial activity and membrane-damaging activity via its effects on membrane structure and membrane-bound mode of PLA2.
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chiou
authors.forename: Shinne-Ren
authors.initials: SR
authors.lastname: Lin
authors.forename: Wan-Ping
authors.initials: WP
authors.lastname: Hu
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000737:chemistry; D004546:Elapid Venoms / Q000201:enzymology*; D017815:Elapidae / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008560:Membrane Fluidity; D008566:Membranes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D054467:Phospholipases A2 / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry; D011485:Protein Binding; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D013109:Sphingomyelins / Q000737:chemistry
chemical_list: D004546:Elapid Venoms; D008081:Liposomes; D010743:Phospholipids; D013109:Sphingomyelins; D002784:Cholesterol; D011794:Quercetin; D054467:Phospholipases A2