Article révisé par les pairs
Résumé : The influence of phorbol esters upon the thermotropic behaviour of multilamellar liposomes formed of dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylcholine (DMPC) was investigated, as a model for possible interferences of the phorbol esters with the phospholipid domain of biological membranes. Both biologically active (TPA, 12-O-tetradecanoylphorbol-13-acetate, PDD, phorbol-12,13-didecanoate) and inactive (4 alpha-PDD, 4 alpha-phorbol-12,13-didecanoate) phorbol esters lowered the temperature required to cause a fall in fluorescence polarization of a fluorescent probe inserted in the lipid matrix of the DMPC or DPPC liposomes and facilitated the process of calcium exchange-diffusion in DPPC liposomes containing the ionophore A23187. Both of these effects could be due to a decrease in viscosity of the liposomal matrix. However, differential scanning calorimetry revealed that the thermotropic changes evoked by each of these phorbol esters were not identical. In most cases, the phorbol esters decreased both the main phase transition temperature and enthalpy of melting. However, when TPA was incorporated in DMPC liposomes, i.e. when a myristoyl chain was present in both the phorbol ester and phospholipid, no change in the enthalpy of melting could be detected, whereas the main phase transition temperature decreased in proportion to the TPA content of the liposomes. These findings emphasize the view that phorbol esters indeed interact with phospholipids and that the characteristics of such an interaction may tightly depend on the precise chemical structure of both the phorbol ester and phospholipid under consideration.