AMINOGLYCOSIDE ANTIBIOTICS PREVENT THE FORMATION OF NONBILAYER STRUCTURES IN NEGATIVELY-CHARGED MEMBRANES - COMPARATIVE-STUDIES USING FUSOGENIC (BIS(BETA-DIETHYLAMINOETHYLETHER)HEXESTROL) AND AGGREGATING (SPERMINE) AGENTS
F. Vanbambeke et al., AMINOGLYCOSIDE ANTIBIOTICS PREVENT THE FORMATION OF NONBILAYER STRUCTURES IN NEGATIVELY-CHARGED MEMBRANES - COMPARATIVE-STUDIES USING FUSOGENIC (BIS(BETA-DIETHYLAMINOETHYLETHER)HEXESTROL) AND AGGREGATING (SPERMINE) AGENTS, Chemistry and physics of lipids, 79(2), 1996, pp. 123-135
Aminoglycoside antibiotics cause aggregation but not fusion of negativ
ely-charged liposomes at an extent proportional to their capacity to i
nteract with acidic phospholipids (Van Bambeke et al., 1995, Eur. J. P
harmacol., 289, 321-333). To understand why aggregation is not followe
d by fusion, we have examined here the influence of two aminoglycoside
s with markedly different toxic potential (gentamicin > isepamicin) on
lipid phase transition in negatively-charged liposomes using P-31-NMR
spectroscopy. in comparison with spermine (an aggregating agent) and
bis(beta-diethylaminoethylether)hexestrol or DEH (a fusogenic cationic
amphiphile). Gentamicin. spermine, and, to a lesser extent, isepamici
n inhibit the appearance of the isotropic signal seen upon warming of
control liposomes and denoting the presence of mobile structures. This
non-bilayer signal appeared most prominently when liposomes were incu
bated with DEH, a strong fusogenic agent. We conclude that aminoglycos
ides, like spermine, have the potential to prevent membrane fusion, by
inhibiting the development of a critical change in membrane organizat
ion, which is associated with fusion. We suggest that this capacity co
uld be a determinant in aminoglycoside toxicity.