Jørgensen Kent, Davidsen Jesper, Mouritsen Ole G
MEMPHYS - Center for Biomembrane Physics, LiPlasome Pharma A/S, Technical University of Denmark, Building 207, DK-2800, Lyngby, Denmark.
FEBS Lett. 2002 Oct 30;531(1):23-7. doi: 10.1016/s0014-5793(02)03408-7.
Secretory phospholipase A2 (PLA2) is a ubiquitous water-soluble enzyme found in venom, pancreatic, and cancerous fluid. It is also known to play a role in membrane remodeling processes as well as in cellular signaling cascades. PLA2 is interfacially active and functions mainly on organized types of substrate, e.g. micelles and lipid bilayers. Hence the activity of the enzyme is modulated by the lateral organization and the physical properties of the substrate, in particular the structure in the nanometer range. The evidence for nano-scale structure and lipid domains in bilayers is briefly reviewed. Results obtained from a variety of experimental and theoretical studies of PLA2 activity on lipid-bilayer substrates are then presented which provide insight into the biophysical mechanisms of PLA2 activation on lipid bilayers and liposomes of different composition. The insight into these mechanisms has been used to propose a novel principle for liposomal drug targeting, release, and absorption triggered by secretory PLA2.
分泌型磷脂酶A2（PLA2）是一种普遍存在的水溶性酶，存在于毒液、胰液和癌性体液中。已知它在膜重塑过程以及细胞信号级联反应中发挥作用。PLA2具有界面活性，主要作用于有组织的底物类型，如胶束和脂质双层。因此，该酶的活性受到底物的侧向组织和物理性质的调节，特别是纳米级别的结构。本文简要回顾了双层膜中纳米级结构和脂质域的证据。然后介绍了从对PLA2在脂质双层底物上的活性进行的各种实验和理论研究中获得的结果，这些结果为PLA2在不同组成的脂质双层和脂质体上的激活生物物理机制提供了见解。对这些机制的深入了解已被用于提出一种由分泌型PLA2触发的脂质体药物靶向、释放和吸收的新原理。
