|
The Journal of Lipid Research, Vol. 40, 1276-1283, July 1999
Copyright © 1999 by Lipid Research, Inc.
Targeted disruption of the murine lecithin:cholesterol acyltransferase gene is associated with reductions in plasma paraoxonase and platelet-activating factor acetylhydrolase activities but not in apolipoprotein J concentration
Trudy M. Fortea,
Michael N. Odaa,
Laura Knoffa,
Balz Freib,
Jung Suhb,
Judith A. K. Harmonyc,
William D. Stuartc,
Edward M. Rubina, and
Dominic S. Nga
a Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94729
b Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331
c Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, 231 Bethesda Avenue, Cincinnati, OH 45267
Correspondence to:
Trudy M. Forte
Lecithin:cholesteryl acyltransferase (LCAT) deficiency resulting from targeted disruption of the Lcat gene in the mouse is associated with dramatic decreases in HDL concentration and the accumulation of nascent HDL in the plasma. We examined whether LCAT deficiency in mice is associated with a concomitant decrease in two antioxidative enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH). In control Lcat (+/+) mice both these enzymes are transported on HDL. Compared to Lcat (+/+) mice, HDL-cholesterol is reduced 94% and apoA-I, 90%, in Lcat (-/-) mice; this reduction in HDL is paralleled by a 71% decrease in PAF-AH activity and in a 58% decrease in PON activity. Apolipoprotein J (apoJ) levels, rather than being decreased, were significantly (P = 0.01) higher (36%) in Lcat (-/-) than in Lcat (+/+) mice, and the apo J/PON ratio was 3-fold greater in Lcat (-/-) than in Lcat (+/+) animals. Even though apolipoprotein A-I (apoA-I) concentration and PON activity were drastically reduced, there was no reduction in apoA-I and PON liver mRNA levels suggesting that post-transcriptional events are responsible for the reduction of plasma PON and apoA-I levels. Fast protein liquid chromatography (FPLC) revealed that in Lcat (+/+) mice both PON and PAF-AH activity is associated with large, apoA-I-containing HDL particles (9.7 nm by non-denaturing gradient gel electrophoresis) while in Lcat (-/-) mice both enzymes are associated with small 8.2 nm particles.
We conclude that the concomitant reduction in HDL and apoA-I concentrations and PON and PAF-AH activities is best explained by rapid clearance of the small HDL particles found in LCAT deficiency.Forte, T. M., M. N. Oda, L. Knoff, B. Frei, J. Suh, J. A. K. Harmony, W. D. Stuart, E. M. Rubin, and D. S. Ng. Targeted disruption of the murine lecithin:cholesterol acyltransferase gene is associated with reductions in plasma paraoxonase and platelet-activating factor acetylhydrolase activities but not in apolipoprotein J concentration. J. Lipid Res. 1999. 40: 1276;1283.
Supplementary key words:
LCAT deficiency, nascent HDL, lipid hydroperoxides, apoA-I, antioxidative enzymes, fast protein liquid chromatography

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
F. Tabet, A. T. Remaley, A. I. Segaliny, J. Millet, L. Yan, S. Nakhla, P. J. Barter, K.-A. Rye, and G. Lambert
The 5A Apolipoprotein A-I Mimetic Peptide Displays Antiinflammatory and Antioxidant Properties In Vivo and In Vitro
Arterioscler Thromb Vasc Biol,
February 1, 2010;
30(2):
246 - 252.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. E. Wergedal, C. L. Ackert-Bicknell, W. G. Beamer, S. Mohan, D. J. Baylink, and A. K. Srivastava
Mapping genetic loci that regulate lipid levels in a NZB/B1NJxRF/J intercross and a combined intercross involving NZB/B1NJ, RF/J, MRL/MpJ, and SJL/J mouse strains
J. Lipid Res.,
August 1, 2007;
48(8):
1724 - 1734.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Bergmeier, R. Siekmeier, and W. Gross
Distribution Spectrum of Paraoxonase Activity in HDL Fractions
Clin. Chem.,
December 1, 2004;
50(12):
2309 - 2315.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. S. Ng, C. Xie, G. F. Maguire, X. Zhu, F. Ugwu, E. Lam, and P. W. Connelly
Hypertriglyceridemia in Lecithin-cholesterol Acyltransferase-deficient Mice Is Associated with Hepatic Overproduction of Triglycerides, Increased Lipogenesis, and Improved Glucose Tolerance
J. Biol. Chem.,
February 27, 2004;
279(9):
7636 - 7642.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. G. Cabana, C. A. Reardon, N. Feng, S. Neath, J. Lukens, and G. S. Getz
Serum paraoxonase: effect of the apolipoprotein composition of HDL and the acute phase response
J. Lipid Res.,
April 1, 2003;
44(4):
780 - 792.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Hatahet, L. Cole, B. J. Kudchodkar, and T. V. Fungwe
Dietary Fats Differentially Modulate the Expression of Lecithin:Cholesterol Acyltransferase, Apoprotein-A1 and Scavenger Receptor B1 in Rats
J. Nutr.,
March 1, 2003;
133(3):
689 - 694.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Boisfer, D. Stengel, D. Pastier, P. M. Laplaud, N. Dousset, E. Ninio, and A.-D. Kalopissis
Antioxidant properties of HDL in transgenic mice overexpressing human apolipoprotein A-II
J. Lipid Res.,
May 1, 2002;
43(5):
732 - 741.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. S. Ng, G. F. Maguire, J. Wylie, A. Ravandi, W. Xuan, Z. Ahmed, M. Eskandarian, A. Kuksis, and P. W. Connelly
Oxidative Stress Is Markedly Elevated in Lecithin:Cholesterol Acyltransferase-deficient Mice and Is Paradoxically Reversed in the Apolipoprotein E Knockout Background in Association with a Reduction in Atherosclerosis
J. Biol. Chem.,
March 29, 2002;
277(14):
11715 - 11720.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. M. Forte, G. Subbanagounder, J. A. Berliner, P. J. Blanche, A. O. Clermont, Z. Jia, M. N. Oda, R. M. Krauss, and J. K. Bielicki
Altered activities of anti-atherogenic enzymes LCAT, paraoxonase, and platelet-activating factor acetylhydrolase in atherosclerosis-susceptible mice
J. Lipid Res.,
March 1, 2002;
43(3):
477 - 485.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Ferre, J. Camps, E. Prats, E. Vilella, A. Paul, L. Figuera, and J. Joven
Serum Paraoxonase Activity: A New Additional Test for the Improved Evaluation of Chronic Liver Damage
Clin. Chem.,
February 1, 2002;
48(2):
261 - 268.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|