PMID- 10479665
OWN - NLM
STAT- MEDLINE
DCOM- 19991007
LR  - 20220316
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 19
IP  - 9
DP  - 1999 Sep
TI  - Human serum Paraoxonase/Arylesterase's retained hydrophobic N-terminal leader
      sequence associates with HDLs by binding phospholipids : apolipoprotein A-I
      stabilizes activity.
PG  - 2214-25
AB  - In serum, human paraoxonase/arylesterase (PON1) is found exclusively associated
      with high density lipoprotein (HDL) and contributes to its antiatherogenic
      properties by inhibiting low density lipoprotein (LDL) oxidation. Difficulties in
      purifying PON1 from apolipoprotein A-I (apoA-I) suggested that PON1's association
      with HDL may occur through a direct binding between these 2 proteins. An unusual 
      property of PON1 is that the mature protein retains its hydrophobic N-terminal
      signal sequence. By expressing in vitro a mutant PON1 with a cleavable
      N-terminus, we demonstrate that PON1 associates with lipoproteins through its
      N-terminus by binding phospholipids directly rather than binding apoA-I.
      Nonetheless, apoA-I stabilized arylesterase activity more than did phospholipid
      alone, apoA-II, or apoE. Consequently, we studied the role of apoA-I in PON1
      expression and HDL association in mice genetically deficient in apoA-I. Though
      present in HDL fractions at decreased levels, PON1 arylesterase activity was less
      stable than in control mice. Furthermore, PON1 could be competitively removed
      from HDL by phospholipids, suggesting that PON1's retained N-terminal peptide
      allows transfer of the enzyme between phospholipid surfaces. Thus, our data
      suggest that PON1 is stabilized by apoA-I, and its binding to HDL and
      physiological distribution are dependent on the direct binding of the retained
      hydrophobic N-terminus to phospholipids optimally presented in association with
      apoA-I.
FAU - Sorenson, R C
AU  - Sorenson RC
AD  - Department of Pharmacology, University of Michigan Medical School, Ann Arbor
      48109, USA.
FAU - Bisgaier, C L
AU  - Bisgaier CL
FAU - Aviram, M
AU  - Aviram M
FAU - Hsu, C
AU  - Hsu C
FAU - Billecke, S
AU  - Billecke S
FAU - La Du, B N
AU  - La Du BN
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Detergents)
RN  - 0 (Lipoproteins)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Peptide Fragments)
RN  - 0 (Phospholipids)
RN  - 0 (Proteolipids)
RN  - 0 (proteoliposomes)
RN  - EC 3.1.- (Esterases)
RN  - EC 3.1.1.- (Carboxylic Ester Hydrolases)
RN  - EC 3.1.1.2 (arylesterase)
RN  - EC 3.1.8.1 (Aryldialkylphosphatase)
RN  - EC 3.1.8.1 (PON1 protein, human)
SB  - IM
MH  - Animals
MH  - Apolipoprotein A-I/*physiology
MH  - Aryldialkylphosphatase
MH  - Binding, Competitive
MH  - Carboxylic Ester Hydrolases/blood/genetics/*metabolism/physiology
MH  - Cell Line
MH  - Cholesterol, HDL/*metabolism
MH  - Detergents/metabolism
MH  - Esterases/blood/genetics/*metabolism/physiology
MH  - Female
MH  - Humans
MH  - Lipoproteins/blood/metabolism
MH  - Lipoproteins, LDL/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidation-Reduction
MH  - Peptide Fragments/genetics/*metabolism/physiology
MH  - Phospholipids/*metabolism/pharmacology
MH  - Proteolipids/metabolism
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.1161/01.atv.19.9.2214 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1999 Sep;19(9):2214-25. doi:
      10.1161/01.atv.19.9.2214.