Pawelczyk T, Lowenstein J M
Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254.
Arch Biochem Biophys. 1992 Sep;297(2):328-33. doi: 10.1016/0003-9861(92)90680-u.
Phospholipase C delta (PLC delta) is strongly inhibited by sphingomyelin (SM). The inhibition occurs in both the presence and the absence of spermine, an activator of PLC delta. Phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylinositol (PI) also inhibit PLC delta in the presence of spermine but are much less effective than SM. PE and PC activate and PS and PI inhibit PLC delta in the absence of spermine. Again, the inhibition by PS and PI is much weaker than the inhibition observed with SM. Similar or identical effects are observed in detergent micelle and liposome assays. Comparisons of physiological concentrations of SM with concentrations yielding 50% inhibition of PLC delta in vitro indicate that SM is likely to be a major factor in regulating the activity of PLC delta by inhibition. It is proposed that, in vivo, sphingomyelin acts as an inhibitor of PLC delta, which enables the enzyme to be regulated by activation. In certain circumstances, there is a substantial decline in SM and this may lead to a partial relief of the inhibition. PLC delta is activated by sphingosine in the absence of spermine. However, this activation occurs at unphysiologically high concentrations of sphingosine. The effects of SM and sphingosine on PLC delta in marked contrast to those observed with protein kinase C, which is unaffected by sphingomyelin and inhibited by sphingosine.
磷脂酶Cδ（PLCδ）受到鞘磷脂（SM）的强烈抑制。无论有无精胺（PLCδ的一种激活剂），这种抑制作用都会发生。在有精胺存在的情况下，磷脂酰乙醇胺（PE）、磷脂酰胆碱（PC）、磷脂酰丝氨酸（PS）和磷脂酰肌醇（PI）也会抑制PLCδ，但效果远不如SM。在没有精胺的情况下，PE和PC会激活PLCδ，而PS和PI则会抑制它。同样，PS和PI的抑制作用比SM观察到的抑制作用要弱得多。在去污剂胶束和脂质体测定中也观察到了类似或相同的效果。将SM的生理浓度与体外产生50% PLCδ抑制作用的浓度进行比较表明，SM可能是通过抑制作用调节PLCδ活性的主要因素。有人提出，在体内，鞘磷脂作为PLCδ的抑制剂，使该酶能够通过激活作用进行调节。在某些情况下，SM会大幅下降，这可能会导致抑制作用部分缓解。在没有精胺的情况下，鞘氨醇会激活PLCδ。然而，这种激活作用发生在非生理浓度的鞘氨醇条件下。SM和鞘氨醇对PLCδ的影响与蛋白激酶C观察到的影响形成鲜明对比，蛋白激酶C不受鞘磷脂影响，但受鞘氨醇抑制。
