Premium
Cationic lipids destabilize lysosomal membrane in vitro
Author(s) -
Wattiaux Robert,
Jadot Michel,
Warnier-Pirotte Marie-Thérèse,
Wattiaux-De Coninck Simone
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01283-0
Subject(s) - cationic polymerization , chemistry , membrane , biochemistry , liposome , phospholipid , cationic liposome , membrane lipids , endosome , organelle , lipid bilayer fusion , enzyme , biophysics , transfection , biology , intracellular , organic chemistry , gene
Addition of cationic lipids to plasmid DNA considerably increases the efficiency of transfection. The mechanism has not yet been elucidated. A possibility is that these compounds destabilize biological membranes (plasma, endosomal, lysosomal), facilitating the transfer of nucleic molecules through these membranes. We have investigated the problem by determining if a cationic lipid N ‐(1‐(2,3‐dioleoxy)propyl)‐ N , N , N ,‐trimethylammonium methyl‐sulfate (DOTAP, Boehringer, Mannheim, Germany) affects the integrity of rat liver lysosomal membrane. We have measured the latency of β‐galactosidase, a lysosomal enzyme, and found that incubation of lysosomes with low concentrations of DOTAP causes a striking increase in free activity of the hydrolase and even a release of the enzyme into the medium. This indicates that lysosomal membrane is deeply destabilized by the lipid. The phenomenon depends on pH, it is less pronounced at pH 5 than at pH 7.4. Anionic compounds, particularly anionic amphipathic lipids, can to some extent prevent this phenomenon. It can be observed with various cationic lipids. A possible explanation is that cationic liposomes interact with anionic lipids of lysosomal membrane, allowing a fusion between the lipid bilayers which results in a destabilization of the organelle membrane.