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Bimodal regulatory effect of melittin and phospholipase A2-activating protein on human type II secretory phospholipase A2.

机译:蜂毒肽和磷脂酶A2激活蛋白对人II型分泌磷脂酶A2的双峰调节作用。

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摘要

Melittin and phospholipase A2-activating protein (PLAP) are known as efficient activators of secretory phospholipase A2(sPLA2) types I, II, and III when phospholipid liposomes are used as substrate. The present study demonstrates that both peptides can either inhibit or activate sPLA2 depending on the peptide/phospholipid ratio when erythrocyte membranes serve as a biologically relevant substrate. Low concentrations of melittin and PLAP were observed to inhibit sPLA2-triggered release of fatty acids from erythrocyte membranes. The inhibition was reversed at melittin concentrations above 1 microM. PLAP-induced inhibition of sPLA2 persisted steadily throughout the used concentration range (0-150 nM). The two peptides induced a dose-dependent activation of sPLA2 at low concentrations, followed by inhibition when model membranes were used as substrate. This opposite modulatory effect on biological membranes and model membranes is discussed with respect to different mechanisms the interaction of the regulatory peptides with the enzyme molecules and the substrate vesicles.
机译:当磷脂脂质体用作底物时,蜂毒肽和磷脂酶A2激活蛋白(PLAP)被称为I,II和III型分泌性磷脂酶A2(sPLA2)的有效激活剂。本研究表明,当红细胞膜用作生物学相关底物时,两种肽均可抑制或激活sPLA2,具体取决于肽/磷脂比率。观察到低浓度的蜂毒肽和PLAP可抑制sPLA2触发的脂肪酸从红细胞膜释放。在蜂毒蛋白浓度高于1 microM时抑制被逆转。 PLAP诱导的sPLA2抑制在整个使用浓度范围(0-150 nM)内持续稳定。这两种肽在低浓度下诱导sPLA2的剂量依赖性活化,然后在将模型膜用作底物时被抑制。关于调节肽与酶分子和底物囊泡相互作用的不同机理,讨论了对生物膜和模型膜的相反调节作用。

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