Serum paraoxonase activity and the extent of lipid peroxidation are not affected by increased levels of human apolipoprotein A-I: studies in transgenic mice.
The present study analyzed the effect of increased concentrations of human apolipoprotein (apo) A-I in transgenic mice serum on paraoxonase activity and on lipid peroxidation. In the transgenic mice serum, in comparison to control (non-transgenic) C57BL/6 mice, we found high concentrations of human apoA-I and high-density lipoprotein (HDL)-cholesterol, but serum lipid peroxidation (basal and free radical-induced) and serum paraoxonase activity were similar in the two mouse groups. Comparing the individual results, no significant correlation was found between free radical-induced serum lipid peroxidation and apoA-I concentrations. Serum paraoxonase activity also did not correlate with serum concentrations of human apoA-I. However, a significant inverse relationship (R2=0.75) was observed between the individual values of paraoxonase activity and free radical-induced lipid peroxidation in both mouse groups. Direct analysis of the effect of pure human apoA-I and paraoxonase (using the specific paraoxonase inhibitor PD-92770) on lipid peroxidation also revealed that paraoxonase, but not apoA-I, protects serum lipids from oxidation. We thus conclude that the increased human apoA-I concentration in the mouse serum neither affect serum paraoxonase activity, nor protects against lipid peroxidation, whereas paraoxonase significantly inhibits serum lipid peroxidation.
Rosenblat
Mira
M
The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel.
Grunfeld
Orit
O
Hayek
Tony
T
Aviram
Michael
M
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood*; D043303:Aryldialkylphosphatase; D008076:Cholesterol, HDL / Q000097:blood; D004950:Esterases / Q000037:antagonists & inhibitors / Q000097:blood* / Q000378:metabolism*; D005609:Free Radicals; D015870:Gene Expression; D006801:Humans; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010084:Oxidation-Reduction
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D005609:Free Radicals; D004950:Esterases; D043303:Aryldialkylphosphatase