Influence of the St. John's Wort extract Ze117 on membrane fluidity, signal transduction, and mobility of the β1-adrenergic receptor

Besides specific ligand and receptor interactions plasma membrane properties also influence cellular signal transduction pathways [1]. Membrane fluidity which is one of these properties can be measured by fluorescence anisotropy. Here we used this technique to determine the influence of the St. John's Wort extract Ze117 on the plasma membrane fluidity of C6 glioblastoma cells. For this purpose DPH (1,6-diphenyl-1,3,5-hexatriene) and TMA-DPH (1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene) were applied probing the rotational microenvironment within the hydrophobic membrane core and close to the membrane/water interface, respectively.

Chronic exposure (6 – 8 days) of C6 cells to Ze117 dose-dependently increased DPH and TMA-DPH fluorescence anisotropy, reflecting a membrane rigidification effect. The in parallel tested antidepressants desipramine and citalopram showed no effect on the membrane fluidity after chronic incubation.

Since changes in membrane fluidity are likely to affect membrane-associated GPCR signal transduction we examined the β₁-adrenergic receptor (β₁-AR) stimulation-mediated cAMP formation after chronic exposure to Ze117. A concentration-dependent reduction in β₁-AR-mediated cAMP formation after stimulation with dobutamine was observed for the Ze117 extract [2].

This observation of a dose-dependent membrane rigidification suggests a reduced lateral receptor mobility, explaining the reduced β₁-AR signaling after chronic exposure of C6 cells to Ze117. Thus, Ze117 might be suitable to reduce stress-mediated β₁-AR signaling by reducing the fluidity of plasma membranes.

[1] Escribá PV, Wedegaertner PB, Goñi FM, Vögler O. Biochim Biophys Acta 2007; 1768: 836 – 852

[2] Data were generated by Anne Hage-Hülsmann at the Institute of Biochemistry and Molecular Biology, Bonn