A mechanism underlying stimulation and inhibition of protein kinase C by lyso-PC: A role of membrane physical state.
Lysophosphatidylcholine (lyso-PC) biphasically regulates the diacylglycerol-induced activation of protein kinase C (PKC). In common parlance, lyso-PC stimulates PKC at low concentrations, but, conversely, inhibits it at high concentrations. The activity of purified PKC from rat brains was measured in the vesicles made up of dipalmitoylphosphatidylserine (DPPS), 1, 2-sn-diolein (DOG) and different molar ratios of 1-palmitoyl-sn-glycerol-3-phosphoryl-choline (C16:0 lyso-PC). The effect, i. e. stimulation or inhibition on PKC by C16:0 lyso-PC, depends on DPPS and DOG concentrations as well as its own concentration. When the concentration of DOG is stable, this C16:0 lyso-PC action depends on C16:0 lyso-PCIDPPS molar ratio. Differential scanning calorimetry (DSC), two fluorescence probes and light scattering were used to analyze the physical characteristics of membrane, including thermotropic phase behavior, the turbidity, the lipid molecular acyl chains packing and the head group spacing. The more adulteration of C16:0 lyso-PC in liposome bilayer membrane, the looser acyl chains pack, and the broader head group spacing. DSC results show that there are two immiscible lipid areas in the membrane: C16:0 lyso-PC-rich area and C16: 0 lyso-PC-poor area. When C16:0 lyso-PC/DPPS molar ratio was 0.234, the two areas had the broadest boundary and the activation of PKC was the highest. When the ratio was over 0.434, the phase transition of DPPS disappeared; micelle tended to substitute the structure of bilayer; the activity of PKC was inhibited completely. DOG can stabilize the bilayer structure of membrane, so the C16:0 lyso-PC/DPPS molar ratios to inhibit PKC in lipid mixture with DOG are higher than that without DOG. The ability of C16:0 lyso-PC to change the physical properties and the structure of membrane plays an important role in its effect on PKC activation.
Pan
Z
Z
Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Chen
J
J