Common variants of apolipoprotein A-IV differ in their ability to inhibit low density lipoprotein oxidation.
Apolipoprotein A-IV (apoA-IV) inhibits lipid peroxidation, thus demonstrating potential anti-atherogenic properties. The aim of this study was to investigate how the inhibition of low density lipoprotein (LDL) oxidation was influenced by common apoA-IV isoforms. Recombinant wild type apoA-IV (100 microg/ml) significantly inhibited the oxidation of LDL (50 microg protein/ml) by 5 microM CuSO(4) (P<0.005), but not by 100 microM CuSO(4), suggesting that it may act by binding copper ions. ApoA-IV also inhibited the oxidation of LDL by the water-soluble free-radical generator 2,2'-azobis(amidinopropane) dihydrochloride (AAPH; 1 mM), as shown by the two-fold increase in the time for half maximal conjugated diene formation (T(1/2); P<0.05) suggesting it can also scavenge free radicals in the aqueous phase. Compared to wild type apoA-IV, apoA-IV-S347 decreased T(1/2) by 15% (P=0.036) and apoA-IV-H360 increased T(1/2) by 18% (P=0.046). All apoA-IV isoforms increased the relative electrophoretic mobility of native LDL, suggesting apoA-IV can bind to LDL and acts as a site-specific antioxidant. The reduced inhibition of LDL oxidation by apoA-IV-S347 compared to wild type apoA-IV may account for the previous association of the APOA4 S347 variant with increased CHD risk and oxidative stress.
Wong
Wai-Man R
WM
Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London, UK.
Gerry
Andrew B
AB
Putt
Wendy
W
Roberts
Jane L
JL
Weinberg
Richard B
RB
Humphries
Steve E
SE
Leake
David S
DS
Talmud
Philippa J
PJ
D000578:Amidines / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics* / Q000502:physiology*; D019327:Copper Sulfate / Q000737:chemistry; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D020033:Protein Isoforms / Q000502:physiology
C437704:APOA5 protein, human; D000578:Amidines; D000975:Antioxidants; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D008077:Lipoproteins, LDL; D020033:Protein Isoforms; C046728:2,2'-azobis(2-amidinopropane); D019327:Copper Sulfate