Wiedendiol-A inhibits cholesteryl ester binding to its transfer protein.
OBJECTIVE
To study the wiedendiol-A (W-A) inhibition mechanism of plasma cholesteryl ester (CE) transfer protein (CETP) on the transfer of CE.


METHODS
Using gel filtration method.


RESULTS
W-A at 30 mumol.L-1 inhibited association of CE with CETP by 76% and CETP transfer activity by 81%. In addition, W-A enhanced binding of TP2, a monoclonal antibody with a CETP C-terminal epitope which is involved in CE binding, to CETP, suggesting a W-A-induced conformational change at the epitope for increased TP2 binding. When CETP activity was measured by varying high-density lipoproteins (HDL) concentration, the apparent Vmax of CE transfer was inhibited by 74% and 83% in the presence of W-A at 14 and 25 mumol.L-1, respectively, while the apparent K(m) of HDL for CETP did not change.


CONCLUSIONS
W-A action is mediated through interaction between W-A and CETP, but not through those between W-A and lipoproteins.
Wang
S
S
Department of CNS/CV Biological Research, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. wang@spcorp.com
Clemmons
A
A
Chackalamannil
S
S
Coval
S J
SJ
Sybertz
E
E
Burrier
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006023:Glycoproteins; D008075:Lipoproteins, HDL / Q000378:metabolism
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL