On the importance of anandamide structural features for its interactions with DPPC bilayers: effects on PLA2 activity

The acylethanolamide anandamide (AEA) occurs in a variety of mammalian tissues and, as a result of its action on cannabinoid receptors, exhibits several cannabimimetic activities. Moreover, some of its effects are mediated through interaction with an ion channel-type vanilloid receptor. However, the chemical features of AEA suggest that some of its biological effects could be related to physical interactions with the lipidic part of the membrane. The present work studies the effect of AEA-induced structural modifications of the dipalmitoylphosphatidylcholine (DPPC) bilayer on phospholipase A2 (PLA2) activity, which is strictly dependent on lipid bilayer features. This study, performed by 2-dimethylamino-(6-lauroyl)-naphthalene fluorescence, demonstrates that the effect of AEA on PLA2 activity is concentration-dependent. In fact, at low AEA/DPPC molar ratios (from R = 0.001 to R = 0.04), there is an increase of the enzymatic activity, which is completely inhibited for R = 0.1. X-ray diffraction data indicate that the AEA affects DPPC membrane structural properties in a concentration-dependent manner. Because the biphasic effect of increasing AEA concentrations on PLA2 activity is related to the induced modifications of membrane bilayer structural properties, we suggest that AEA-phospholipid interactions may be important to produce, at least in part, some of the similarly biphasic responses of some physiological activities to increasing concentrations of AEA

Correlation between functional and structural changes of reduced and oxidized trout hemoglobins I and IV at different pHs. A circular dichroism study.

Circular dichroism (CD) spectra of two major hemoglobin components (Hb), HbI and HbIV, from Oncorhyncus mykiss (formerly Salmo irideus) trout were evaluated in the range 250–600 nm. HbI is characterized by a complete insensitivity to pH changes, while HbIV presents the Root effect. Both reduced [iron(II) or oxy] and oxidized (met) forms of the two proteins were studied at different pHs, 7.8 and 6.0, to obtain information about the pH effects on the structural features of these hemoglobins. Data obtained show that oxy and met-HbI are almost insensitive to pH decrease, remaining in the R conformational state also at low pH. On the contrary, the pH decrease induces similar structural changes, characteristics of ligand dissociation and R fi T transition, both in the reduced and in the oxidized HbIV. The structural changes, monitored by CD, are compared with the peroxidative activity of iron(II)-Hb and met-Hb forms and with the superoxide anion scavenger capacity of the proteins