Synovial phospholipase

Synovial Phospholipase A and Inflammatory Response in Mice, Life Sci. 54, 333-338. 

Gil B, Sanz MJ, Terencio MC et al (1994) Effects of flavonoids on Naja naja and human recombinant synovial phospholipase A2 and inflammatory responses in mice. Life Sci 54 PL333-PL338... 

Although extraction of lipids from membranes can be induced in atomic force apparatus (Leckband et al., 1994) and biomembrane force probe (Evans et al., 1991) experiments, spontaneous dissociation of a lipid from a membrane occurs very rarely because it involves an energy barrier of about 20 kcal/mol (Cevc and Marsh, 1987). However, lipids are known to be extracted from membranes by various enzymes. One such enzyme is phospholipase A2 (PLA2), which complexes with membrane surfaces, destabilizes a phospholipid, extracts it from the membrane, and catalyzes the hydrolysis reaction of the srir2-acyl chain of the lipid, producing lysophospholipids and fatty acids (Slotboom et al., 1982 Dennis, 1983 Jain et al., 1995). SMD simulations were employed to investigate the extraction of a lipid molecule from a DLPE monolayer by human synovial PLA2 (see Eig. 6b), and to compare this process to the extraction of a lipid from a lipid monolayer into the aqueous phase (Stepaniants et al., 1997). 

A. indica L. Indian Aristolochia, also known as Indian birthwort, ishvara (Sanskrit), or adagam (Tamil), is a bitter climber native to India. The medicinal material consists of the rhizome, which is to resolve inflammation (India), counteract insect poison, and as an antipyretic (Philippines and Vietnam). The rhizome contains aristolochic acid, which inhibits in vitro and dose-dependent phospholipid hydrolysis by the human synovial fluid phospholipase A2, snake venom phospholipase A2, porcine pancreatic phospholipase A2, and human platelet phospholipase A2 (2). 

Vishwanath BS, Fawzy AA, Franson R, et al. Edema-inducing activity of phospholipase A2 purified from human synovial fluid and inhibition by aristolochic acid. Inflammation 1988 12 549-561. 

Ortiz, A.R., Pastor, M., Palomer, A., Cruciani, G., Gago, F., and Wade, R.C. Reliability of comparative molecular field analysis models effects of data scaling and variable selection using a set of human synovial fluid phospholipase A2 inhibitors. /. Med. Chem. 1997, 40, 1136-1148. 

Selected entries from Methods in Enzymology [vol, page(s)] Cobra venom phospholipase A2 Naja naja naja, 197, 359 phospholipase A2 from rat liver mitochondria, 197, 365 assay and purification of phospholipase A2 from human synovial fluid in rheumatoid arthritis, 197, 373 purification of mammalian nonpan-creatic extracellular phospholipases A2, 197, 381 spleen phospholipases A2, 197, 390 purification and characterization of cytosolic phospholipase A2 activities from canine myocardium and sheep platelets, 197, 400. 

Kawauchi, Y., J. Takasaki, and Y.M. Matsuura. 1994. Preparation and characterization of human rheumatoid arthritic synovial fluid phospholipase A2 produced by recombinant baculovirus-infected insect cells. J Biochem 116 82. 

G6. Gronroos, J. M., and Nevalainen, T. J., Increased concentrations of synovial-type phospholipase A2 in serum and pulmonary and renal complications in acute pancreatitis. Digestion 52,232-236 (1992). 

The best explored mammalian phospholipase Az is the type 114 kDa pancreatic enzyme released as a proenzyme. Tike 14 kDa phospholipases have been clafr-siiied utilizing evolutionary relationships into type i (in pancreas juice), type D (in platelets, synovial fluid), and type lH (in bee venom). Platelets and macrophages contain intracellulariy a structurally different 85 kDa phospholipase type IV. 

M. T. Pisabarro, A.R. Ortiz, A. Palomer, F. Cabre, L. Garcia, R.C. Wade, F. Gago, D. Mauleon, G. Carganico, Rational Modification of Human Synovial Fluid Phospholipase A2 Inhibitors,/. Med. Chem. 1994, 37, 337-341. 

LaiCY,andWadaK. (1988). Phospholipase A, fixan human synovial fluid purification and structural homology to the placental enzyme. Biodion Biophys Res Commun 137 488-493. 

Seilhamer JJ, Pruzanski W, and Vada P. (Other authors). (1989). Chadngandrecondnnanteiqaession of phospholipase A, present in rheumatoid arthritic synovial fluid. J Biol Qiem 264 3333-3338. 

Seilhamer, J. J., Pruzanski, W., Vadas, P., Plant, S., Miller, J. A., Kloss, J., and Johnson, L. K. (1989). Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid, y. Biol. Chem. 264, 5335-5338. 

In a validation study, we successfuUy applied LUDI to the design of inhibitors of dihydrofolate reductase and HIV-protease [56]. Pisabarro et al. [62] used a combination of GRID and LUDI to successfully design novel inhibitors of human synovial fluid phospholipase A2 with enhanced activity. A calculation with GRID pointed to a lipophilic binding pocket not occupied by the lead compound. LUDI was then used to search for suitable substituents to fill this pocket. One suggestion from LUDI was synthesized and found to yield a ten-fold improvement in binding affinity. 

Jacobson, P.B., Marshall, L.A., Sung, A., and Jacobs, R.S. (1990) Inactivation of human synovial fluid phospholipase A2 by the marine natural product manoalide. Biochem. Pharmacol., 39, 1557-1564. 

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