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A mechanism underlying stimulation and inhibition of protein kinase C by lyso-PC: A role of membrane physical state

A mechanism underlying stimulation and inhibition of protein kinase C by lyso-PC: A role of membrane physical state
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摘要 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 PC/DPPS 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. 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 PC/DPPS 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.
作者 潘最 陈建文
出处 《Science China(Life Sciences)》 SCIE CAS 1998年第6期584-591,共8页 中国科学(生命科学英文版)
基金 theNationalNaturalScienceFoundationofChina (GrantNo .39730 130 )
关键词 protein KINASES C LYSOPHOSPHATIDYLCHOLINE diolein differential scanning CALORIMETRY physical properties of membrane. protein kinases C, lysophosphatidylcholine, diolein, differential scanning calorimetry, physical properties of membrane.
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