Antioxidant properties of HDL in transgenic mice overexpressing human apolipoprotein A-II.
Transgenic mice overexpressing human apolipoprotein A-II (huapoA-II) display high VLDL and low HDL levels. To evaluate the antioxidant potential of huapoA-II enriched HDL, we measured the activities of paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH). Both activities decreased up to 43% in the serum of transgenic mice compared with controls, varied in parallel to HDL levels, but decreased less than HDL levels. The major part of PON and PAF-AH was associated with HDL, except in fed high huapoA-II-expressing mice, in which 20% of PAF-AH and 9% of PON activities were associated with VLDL. PON mRNA levels in the liver, its major site of synthesis, were similar in transgenic and control animals, indicating normal enzyme synthesis. In transgenic mice, the basal oxidation of lipoproteins was not increased, whereas their VLDL were more susceptible to oxidation than VLDL of controls. Interestingly, HDL of transgenic mice protected VLDL from oxidation more efficiently than HDL of controls. In conclusion, the decrease in both PON and PAF-AH activities in huapoA-II transgenic mice is best explained by their lower plasma HDL levels. However, the unchanged basal lipoprotein oxidation in transgenic mice suggests that huapoA-II-rich HDL may maintain adequate antioxidant potential.
Boisfer
Elisabeth
E
Inserm Unité 505 and Université Paris VI, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Stengel
Dominique
D
Pastier
Danièle
D
Laplaud
P Michel
PM
Dousset
Nicole
N
Ninio
Ewa
E
Kalopissis
Athina-Despina
AD
D000818:Animals; D000975:Antioxidants; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics*; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics; D043303:Aryldialkylphosphatase; D002851:Chromatography, High Pressure Liquid; D004950:Esterases / Q000097:blood; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D010972:Platelet Activating Factor / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012016:Reference Values
D000975:Antioxidants; D016633:Apolipoprotein A-II; D001053:Apolipoproteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010972:Platelet Activating Factor; C099252:oxidized low density lipoprotein; D004950:Esterases; D043303:Aryldialkylphosphatase