Inhibition of phospholipase A 2 in rat brain modifies different membrane fluidity parameters in opposite ways

摘要

Fluidity is an important neuronal membrane property and it is influenced by the concentration of polyunsaturated fatty acids (PUFAs) in membrane phospholipids. Phospholipase A 2 (PLA 2) is a key enzyme in membrane phospholipid metabolism, generating free PUFAs. In Alzheimer disease (AD), reduced PLA 2 activity, specifically of calcium-dependent cytosolic PLA 2 (cPLA 2) and calcium-independent intracellular PLA 2 (iPLA 2), and phospholipid metabolism was reported in the frontal cortex and hippocampus. This study investigated the effects of in vivo infusion of the dual cPLA 2 and iPLA 2 inhibitor MAFP into rat brain on PLA 2 activity and membrane fluidity parameters in the postmortem frontal cortex and dorsal hippocampus. PLA 2 activity was measured by radioenzymatic assay and membrane fluidity was determined by fluorescence anisotropy technique using three different probes: DPH, TMA-DPH, and pyrene. MAFP significantly inhibited PLA 2 activity, reduced the flexibility of fatty acyl chains (indicated by increased DPH anisotropy), increased the fluidity in the lipid-water interface (indicated by decreased TMA-DPH anisotropy), and increased the lipid lateral diffusion in the hydrocarbon core (represented by pyrene excimer formation) of membranes in both brain areas. The findings suggest that reduced cPLA 2 and iPLA 2 activities in AD brain might contribute to the cognitive impairment, in part, through alterations in membrane fluidity parameters.