Nature of the Interaction of Dextran Sulfate with Low Density Lipoproteins of Plasma

Abstract

Abstract The nature of the interaction between dextran sulfate and low density human plasma lipoproteins of the Sf 0 to 10 class (LDL) was investigated by modifying LDL with succinic anhydride or acetic anhydride. In the absence of divalent metal ions, the formation of insoluble and soluble dextran sulfate-LDL complexes was prevented by the acylation of approximately 16% and 25%, respectively, of the LDL free amino groups. The decrease in the positive charges of the protein moiety was primarily responsible for the interference with the complex formation. An increase in the negative charges introduced by succinylation did not interfere as extensively as the reduction in positive charges. The presence of magnesium sulfate facilitated the conversion of succinylated and acetylated lipoproteins to insoluble complex. The amount of Mg++ required for the conversion progressively increased with increases in the extent of acylation. Although the succinylated LDL required more Mg++ than the acetylated LDL, the difference was relatively small until approximately 75% of the lipoprotein amino groups was modified. A steep increase in the magnesium requirement observed upon further increase in the extent of succinylation reflected an extensive increase in negative charges due to succinylation of LDL free hydroxyl groups. The evaluation of the requirement for Mg++ by acetylated and succinylated LDL revealed the involvement of both LDL positive and negative charges in the formation of insoluble complex in the presence of divalent metal ions. Although the treatment of LDL with phospholipase C hydrolyzed as much as 56% of the phospholipids, the LDL was almost completely converted to insoluble complex in both the presence and absence of Mg++. Since minor modification by succinylation or acetylation drastically reduced the reactivity of LDL with dextran sulfate, the protein-charged groups rather than the phospholipid-charged groups seem to play the major role in the dextran sulfate-LDL interaction.