Oxidized phospholipid content destabilizes the structure of reconstituted high density lipoprotein particles and changes their function.
High density lipoprotein (HDL) particles are made up of lipid and protein constituents and apolipoprotein A-I (apoA-I) is a principal protein component that facilitates various biological activities of HDL particles. Increase in Ox-PL content of HDL particles makes them 'dysfunctional' and such modified HDL particles not only lose their athero-protective properties but also acquire pro-atherogenic and pro-inflammatory functions. The details of Ox-PL-induced alteration in the molecular properties of HDL particles are not clear. Paraoxonase 1 (PON1) is an HDL-associated enzyme that possesses anti-inflammatory and anti-atherogenic properties; and many of the athero-protective functions of HDL are attributed to the associated PON1. In this study we have characterized the physicochemical properties of reconstituted HDL (rHDL) particles containing varying amounts of Ox-PL and have compared their PON1 stimulation capacity. Our results show that increased Ox-PL content (a) modifies the physicochemical properties of the lipid domain of the rHDL particles, (b) decreases the stability and alters the conformation as well as orientation of apoA-I molecules on the rHDL particles, and (c) decreases the PON1 stimulation capacity of the rHDL particles. Our data indicate that the presence of Ox-PLs destabilizes the structure of the HDL particles and modifies their function.
Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Punjab, India.
Subhabrata
S
Kar
Mitulkumar A
MA
Patel
Rajan K
RK
Tripathy
Priyanka
P
Bajaj
Unnati V
UV
Suvarnakar
Abhay H
AH
Pande
D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000737:chemistry* / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D010743:Phospholipids; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human