Liposome phospholipase

Jensen SS, Andresen TL, Davidsen J, et al. Secretory phospholipase A2 as a tumor-specific trigger for targeted delivery of a novel class of liposomal prodrug anticancer ether lipids. Mol Cancer Ther 2004 3 1451-1458. 

Van Deenen and colleagues have shown (Biochim. Biophys. Acta 406, 169, 1975) that the activity of a phospholipase against phosphatidylcholine liposomes has a sharp temperature maximum at the phase transition temperature. In addition, Linden et al. (Proc. Natl. Acad. Sci. US 70, 2271, 1973) showed a marked temperature dependence of sugar transport into E. Coli fatty acid auxotrophs at the temperature corresponding to the onset of phase separations of the lipids. 

Jett, M. and Alving, C. R. (1988). Phospholipase A2 substrates a novel approach to cancer chemotherapy. In Liposomes as Drug Carriei Bregoriadis, G, ed.), Wiley, Chichester, pp. 419-429. 

Andresen T. L. and Jorgensen K. (2005). Synthesis and membrane behavior of a new class of unnatural phospholipid analogs useful as phospholipase A2 degradable liposomal drug carriers. Biochim. Biophys. Acta Biomembr. 1669 1-7. 

The second cause may be due to steric hinderance of neighboring components within the myelin sheath. However, we found that digestion of trypsin or phospholipase C cannot alleviate the problem. In addition, hypotonic treatment of myelin which affects the integrity of the bilayer and also causes the splitting of the lamellae at the external apposition (19, 20), did not result in the oxidation of the cerebrosides. Even cerebrosides in liposomes made from pure phosphatidyl choline could not be oxidized. Incidentally, this finding also contradicts Linington and Rumsby who reported significant oxidation of cerebrosides in liposomes made from myelin lipids. 

Andresen TL, Jensen SS, Kaasgaard T, Jorgensen K. Triggered activation and release of liposomal prodmgs and drugs in cancer tissue by secretory phospholipase A2. Curr Drug Deliv. 2005 2 353-362. 

The exact function of the annexin fold family is at present unclear. All of these proteins appear to show calcium-dependent binding to phosphatidylethanolamine or phosphatidylinositol liposomes. In addition, they can promote fusion of liposomes, and because of this property, it has been suggested that these proteins might mediate calcium dependent exocytosis. P36 and p35 have also been shown to bind to F-actin and spectrin [65,66]. Recently, Khanna et al. [70] have reported a procedure for the simultaneous purification of p35, p36 oligomer and p36 monomer from bovine lung, and identified all three proteins as substrates of protein kinase C. Furthermore, the work of Huang et al. [86] and Khanna et al. [69] has suggested that all three proteins are inhibitors of phospholipase A2. Further experiments will be required to clarify the function of these proteins. 

B) - The enzymatic hydrolysis of P-acyls of dilinoleoylphosphatidilcholine (DLPC) in the liposomal membrane by phospholipase A from Apis melifera venom (1), hydrolysis rate of unoxidized DLPC liposomes (2), hydrolysis rate of DLPC liposomes which preliminarv was oxidized by C-l rabbit... 

Homogeneous liposome immunoassays using lytic agents other than complement and mellitin have also been used. Phospholipase C catalyzes the dephosphorylation of phospholipids, which in turn destabilizes the liposome. The assay is based on the inhibition of the lytic activity by an antibody binding to an antigen conjugated to phospholipase Gentamicin is analyzed by this method. 

Role for Secretory Phospholipase A2 (SPLA2) in Liposomal Drug Delivery... 

K. Jorgensen, J. Davidsen, and O.G. Mouritsen. Biophysical mechanisms of phospholipase A2 activation and their use in liposome-based drug delivery. FEBS Lett., 2002, 531, 23-27. 

J. Davidsen, K. Jorgensen, T. L. Andresen, and O.G. Mouritsen. Secreted phospholipase A2 as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue. Biochim. Biophys. Acta,... 

C. Vermehren,T. Keibler, 1. Hylander, T. Hunger Callisen, and K. Jurgensen. Increase in phospholipase A2 activity towards lipopolymer containing liposomes. Biochim. Biophys. Acta, 1998, 1373, 27]-36. 

K. Jurgensen, C. Vermehren, and O.G. Mouritsen. Enhancement of phospholipase A2 catalyzed degradation of polymer grafted PEG-liposomes effects of lipopolymer concentration and chain length. Pharm. Res., 1999, 16, 1493-1495. 

T.L. Andresen, O.G. Mouritsen, M. Begtrup, and K. Jorgensen. Phospholipase A2 activity dependence on liposome surface charge and polymer coverage. Biophys. J., 2002, 82, 148a. 

Phospholipase cleavage of glycosylphosphatidylinositol reconstituted in liposomal membranes. FEBS Lett.., 1998, 432, 150-154. 

Gupta, C. M. and Bali, A. (1981) Carbamyl analogs of phosphatidylcholines synthesis, interaction with phospholipases and permeability behaviour of their liposomes. Biochim. Biophys. Acta 663, 506-515. 

It is concluded that under equihbrium conditions Upids do not easily undergo transbilayer movement in liposomes or membranes [149-151]. On the other hand, phospholipids and cholesterol have been shown to undergo transmembrane movement in erythrocytes under non-equilibrium conditions or following membrane perturbation such as ghost formation or phospholipase treatment [152-154]. More recently Lange and co-workers have made studies of the rate of transmembrane movement of cholesterol in the membranes of human erythrocytes. Normally, cholesterol in intact erythrocytes is not accessible to cholesterol oxidase [155]. 

Studies of the kinetics of pancreatic phospholipase A2 hydrolysis in a phosphatidylcholine bilayer modified by alkyl(en)ylresorcinol homologues also suggests the same possibility. It was shown that 5-n-heptadecyl and 5-n-heptadecenyl resorcinols when incorporated into liposomal membranes at a concentration of 4 mol%, and lower, caused a drastic increase of the latency phase of the enzyme, the period of time during which redistribution of the products within the bilayer occurs... 

Preparation of Phospholipids and Liposomes, sn-2 DHA-inserted phosphatidylcholine (2-DHA-PC) was enzymatically synthesized from soy lysophosphatidylcholine via phospholipase (PL)A2-mediated esterification as previously reported (5). Then, sn-2 DHA-inserted phosphatidylserine (2-DHA-PS) was prepared from 2-DHA-PC through PLD-mediated transphosphatidylation (6). Liposomes with 70%... 

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