Cholesterol inhibits the lytic activity of melittin in erythrocytes

Although cell lysis by the hemolytic peptide, melittin, has been extensively studied, the role of specific lipids of the erythrocyte membrane on melittin-induced hemolysis remains unexplored. In this report, we have explored the modulatory role of cholesterol on the hemolytic activity of melittin by specifically depleting cholesterol from rat erythrocytes using methyl-p-cyclodextrin (M beta CD). Our results show that the hemolytic activity of melittin is increased by similar to 3-fold upon depletion of erythrocyte membrane cholesterol by similar to 55% without any appreciable loss of phospholipids. This result constitutes the first report demonstrating that the presence of cholesterol inhibits the lytic activity of melittin in its natural target membrane, i.e., the erythrocyte membrane. These results are relevant in understanding the role of cholesterol in the mechanism of action of melittin in the erythrocyte membrane. (c) 2005 Elsevier Ireland Ltd. All rights reserved.