Plasma phospholipid transfer protein-mediated reactions are impaired by hypochlorite-modification of high density lipoprotein.
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.
Pussinen
Pirkko J
PJ
Institute of Dentistry, University of Helsinki, P.O. Box 63, FIN-00014, Helsinki, Finland. pirkko.pussinen@helsinki.fi
Metso
Jari
J
Keva
Ritva
R
Hirschmugl
Birgit
B
Sattler
Wolfgang
W
Jauhiainen
Matti
M
Malle
Ernst
E
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
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