title: Plasma phospholipid transfer protein-mediated reactions are impaired by hypochlorite-modification of high density lipoprotein.
abstract: The two main functions of phospholipid transfer protein (PLTP) are the transfer of phospholipids between plasma lipoproteins and the conversion of high density lipoprotein (HDL), where prebeta-HDL particles are generated. HDL is considered an anti-atherogenic lipoprotein due to its function in the reverse cholesterol transport, where prebeta-HDL accepts cellular membrane cholesterol from peripheral tissues. However, the anti-atherogenic properties of native HDL may be abolished by oxidation/modification. Hypochlorous acid/hypochlorite (HOCl/OCl-)-a potent oxidant generated in vivo only by the myeloperoxidase-H2O2-chloride system of activated phagocytes-alters the physiological properties of HDL by generating a pro-atherogenic lipoprotein particle. Therefore, we have studied the effect of HOCl on the function of HDL subclass 3 (HDL3) and triglyceride-enriched HDL3 (TG-HDL3) in PLTP-mediated processes in vitro. Modification of HDL3 and TG-HDL3 with increasing HOCl concentrations (oxidant:lipoprotein molar ratio between 25:1 and 200:1) decreased the capacity of the corresponding lipoprotein particles to accept phospholipids. Although binding of PLTP to unmodified and HOCl-modified lipoprotein particles was similar, the degree of PLTP-mediated HDL conversion was decreased upon HOCl oxidation. PLTP released apolipoprotein A-I (apoA-I) from HOCl-modified HDL3, but the particles formed displayed no prebeta-mobility. Based on these findings, we conclude that the substrate properties of HOCl-modified HDL3 and TG-HDL3 in PLTP-mediated processes are impaired, which indicates that the anti-atherogenic properties of HDL are impaired.
authors.affiliation: Institute of Dentistry, University of Helsinki, P.O. Box 63, FIN-00014, Helsinki, Finland. pirkko.pussinen@helsinki.fi
authors.forename: Pirkko J
authors.initials: PJ
authors.lastname: Pussinen
authors.forename: Jari
authors.initials: J
authors.lastname: Metso
authors.forename: Ritva
authors.initials: R
authors.lastname: Keva
authors.forename: Birgit
authors.initials: B
authors.lastname: Hirschmugl
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sattler
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Ernst
authors.initials: E
authors.lastname: Malle
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D053440:Lipoproteins, HDL3; D008565:Membrane Proteins / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D049294:Phospholipid Transfer Proteins; D011485:Protein Binding / Q000187:drug effects; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D014280:Triglycerides; D006997:Hypochlorous Acid