Gewählte Publikation:
Pussinen, PJ; Metso, J; Keva, R; Hirschmugl, B; Sattler, W; Jauhiainen, M; Malle, E.
Plasma phospholipid transfer protein-mediated reactions are impaired by hypochlorite-modification of high density lipoprotein.
Int J Biochem Cell Biol. 2003; 35(2):192-202
Doi: 10.1016/S1357-2725(02)00130-9
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- Co-Autor*innen der Med Uni Graz
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Hirschmugl Birgit
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Malle Ernst
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Sattler Wolfgang
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- 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.
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Apolipoprotein A-I - chemistry
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Carrier Proteins - blood
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Dose-Response Relationship, Drug - blood
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Humans - blood
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Hypochlorous Acid - chemistry
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Lipoproteins, HDL - chemistry
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Lipoproteins, HDL3 - chemistry
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Membrane Proteins - blood
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Oxidation-Reduction - drug effects
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Phospholipid Transfer Proteins - drug effects
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Protein Binding - drug effects
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Triglycerides - chemistry
- Find related publications in this database (Keywords)
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PLTP
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HDL conversion
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oxidized/modified HDL
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pre beta-HDL
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apoA-I
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phospholipid