PMID- 10393212
OWN - NLM
STAT- MEDLINE
DCOM- 19990804
LR  - 20161124
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 40
IP  - 7
DP  - 1999 Jul
TI  - 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.
PG  - 1276-83
AB  - 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.
FAU - Forte, T M
AU  - Forte TM
AD  - Life Sciences Division, Lawrence Berkeley National Laboratory, University of
      California, Berkeley, CA 94729, USA.
FAU - Oda, M N
AU  - Oda MN
FAU - Knoff, L
AU  - Knoff L
FAU - Frei, B
AU  - Frei B
FAU - Suh, J
AU  - Suh J
FAU - Harmony, J A
AU  - Harmony JA
FAU - Stuart, W D
AU  - Stuart WD
FAU - Rubin, E M
AU  - Rubin EM
FAU - Ng, D S
AU  - Ng DS
LA  - eng
GR  - HL 18574/HL/NHLBI NIH HHS/United States
GR  - HL 27333/HL/NHLBI NIH HHS/United States
GR  - NIH 56170/PHS HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Clu protein, mouse)
RN  - 0 (Clusterin)
RN  - 0 (Glycoproteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (RNA, Messenger)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.3.1.43 (Phosphatidylcholine-Sterol O-Acyltransferase)
RN  - EC 3.1.- (Esterases)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.47 (1-Alkyl-2-acetylglycerophosphocholine Esterase)
RN  - EC 3.1.8.1 (Aryldialkylphosphatase)
SB  - IM
MH  - 1-Alkyl-2-acetylglycerophosphocholine Esterase
MH  - Animals
MH  - Apolipoprotein A-I/blood
MH  - Aryldialkylphosphatase
MH  - Cholesterol/blood
MH  - Clusterin
MH  - Esterases/*blood
MH  - Glycoproteins/*metabolism
MH  - Lipid Peroxidation
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Mice, Knockout
MH  - *Molecular Chaperones
MH  - Phosphatidylcholine-Sterol O-Acyltransferase/*genetics
MH  - Phospholipases A/*metabolism
MH  - Platelet Activating Factor/*metabolism
MH  - RNA, Messenger/metabolism
EDAT- 1999/07/07 00:00
MHDA- 1999/07/07 00:01
CRDT- 1999/07/07 00:00
PHST- 1999/07/07 00:00 [pubmed]
PHST- 1999/07/07 00:01 [medline]
PHST- 1999/07/07 00:00 [entrez]
PST - ppublish
SO  - J Lipid Res. 1999 Jul;40(7):1276-83.