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Tetranitromethane modification of HDL: cross-linking as a possible mechanism for the inhibition of specific HDL binding to membranes

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6065455
Treatment of HDL with tetranitromethane (TNM) inhibits the lipoprotein's specific binding to cells and isolated membranes. TNM causes the nitration of tyrosine residues, and the cross-linking of apoproteins to each other and to lipids in HDL particles. They recently showed that cross-linking of apoproteins to phospholipids was not responsible for the inhibition of binding. To determine the role of cross-linking of apoproteins to each other in the inhibition, they used the bifunctional reagent dimethyl suberimidate (DMS) to cross-link the apoproteins in human HDL/sub 3/. Over 80% of apoproteins in DMS-HDL/sub 3/ were cross-linked, as analyzed by SDS-PAGE. However, DMS-HDL/sub 3/ was similar to control HDL/sub 3/ in its lipid composition and size distribution. As determined by competitive binding with /sup 125/I-HDL/sub 3/, DMS-HDL/sub 3/ was almost completely unable to bind specifically to rat liver plasma membranes. These results suggest that cross-linking of apoproteins to each other is the mechanism by which TNM treatment inhibits the specific binding of HDL to membranes.
Research Organization:
Medical College of Pennsylvania, Philadelphia
OSTI ID:
6065455
Report Number(s):
CONF-870644-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
Country of Publication:
United States
Language:
English

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