Cationic lipids destabilize lysosomal membrane in vitro

FEBS Letters

Warnier-Pirotte, Marie-Thérèse¹  Jadot, Michel¹  Wattiaux, Robert¹  Wattiaux-De Coninck, Simone¹ 

[1] Laboratoire de Chimie Physiologique, Facultés Universitaires Notre-Dame de la Paix, 61, rue de Bruxelles, B-5000 Namur, Belgium

关键词: Cationic lipid;    Lysosomal membrane destabilization;   

DOI  :  10.1016/S0014-5793(97)01283-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown