Phospholipase A2 Activity

Activation of Mi, M3, and M5 mAChRs does not only lead to the generation of IP3 followed by the mobilization of intracellular Ca2+, but also results in the stimulation of phospholipase A2, phospholipase D, and various tyrosine kinases. Similarly, M2 and M4 receptor activation does not only mediate the inhibition of adenylyl cyclase, but also induces other biochemical responses including augmentation of phospholipase A2 activity. Moreover, the stimulation of different mAChR subtypes is also linked to the activation of different classes of mitogen-activated protein kinases (MAP kinases), resulting in specific effects on gene expression and cell growth or differentiation. 

CHOI J H, CHA B K and RHEE s J (1998) Effects of green tea catechin on hepatic microsomal phospholipase A2 activities and changes of hepatic phospholipid species in streptozotocin-induced diabetic rats , JNutr Sci Vitaminol (Tokyo), 44 (5), 673-83. 

Cellular lipoxygenases have been implicated as possible enzymatic mediators of endothelial cell-dependent oxidation of LDL. Inhibitors of lipoxygenase, but not cyclooxygenase, have been shown to be effective inhibitors of LDL oxidation using rabbit endothelial cells (Parthasarathy etal., 1989). Interestingly, a phospholipase A2 activity intrinsic to apo-B has also been implicated in the endothelial cell-dependent modification of LDL (Parthasarathay et al., 1985). 

Parthasarathy, S., Steinbrecher, U.P., Barnett, J., Witztum, J.L. and Steinberg, D. (1985). Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc. Natl Acad. Sci. USA 82, 3000-3004. 

One of the most exiting findings in this area is perhaps the isolation of Bt-CD, a neoclerodane diterpenoid from Baccharis trimera (Less) DC or carqueja (Brazil) used to treat rheumatism and diabetes that shows anti-phospholipase A2 activity (11). Note also the anti-phospholipase A2 and anti-inflammatory activity of Santolina chamaecy-parissus (12). Cirsium japonicum DC, Crossotephium chinense L. Makino, Inula chinensis Rupr. ex Maxim., and Sigesbeckia orientalis L. are used in Asia for the treatment of inflammatory conditions. 

Wichmann, O., Wittbrodt, J. and Schultz, C. (2006). A small-molecule FRET probe to monitor phospholipase A2 activity in cells and organisms. Angew. Chem. Int. Ed. 45, 508-512. 

Holland et al. [125] have shown that the potent vascular smooth muscle cell mitogen and phospholipase A2 activator thrombin stimulated superoxide production in human endothelial cells, which was inhibited by the NADPH oxidase inhibitors. Similarly, thrombin enhanced the production of oxygen species and the expression of )Alphos and Rac2 subunits of NADPH oxidase in VSMCs [126,127]. Greene et al. [128] demonstrated that the activator of NO synthase neuropeptide bradykinin is also able to stimulate NADPH oxidase in VSMCs. Similar to XO, NADPH oxidase enhanced superoxide production in pulmonary artery smooth muscle cells upon exposure to hypoxia [129]. 

Another series of probes which has attracted much interest in membrane studies has been the 2-A-(4-nitrobenzo-2-oxa-l,3-diazole) (NBD)-labeled lipids. These have been used for studies of the lipid trafficking in intact cells using mainly fluorescence microscopic techniques(77), for fluorescence quenching 78-791 and for studies of phospholipase A2 activities in membranes.(80) To date, they have received less attention in the study of lipid dynamics. 

Rashba-Step, J., Tatoyan, A., Duncan, R,. Ann, D., Pushpa-Rehka, T.R., and Sevanian, A, 1997, PhosphoUpid peroxidation induces cytosolic phospholipase A2 activity membrane effects versus enzyme phosphorylation, Arcii. Biochem. Biophys. 343 44-54. 

The acid-soluble SH-groups in platelets are mainly those of glutathione (GSH). GSH is a cofactor for enzymes such as peroxidase. If feverfew is able to interfere with this cofactor, enzyme function may be impaired. One pathway that may be affected in this way is the metabolism of arachidonic acid (Figure 6.1). In the presence of feverfew extract an increase was found in lipoxygenase product formation and impaired conversion of HPETE to HETE, for which GSH is a cofactor [52]. Inhibition of the liberation of [ " C]arachidonic acid from phospholipids was also found [53], which implies impairment of phospholipase A2 activity and for which SH-groups are thought to be important. 

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. 

Glende EA, Recknagel RO. 1992. Phospholipase A2 activation and cell injury in isolated rat hepatocytes exposed to bromotrichloromethane, chloroform, and 1,1-dichloroethylene as compared to effects of carbon tetrachloride. Toxicol AppI Pharmacol 113 159-162. 

Sultan, C., A. Terraza, E. Carilla, M. Briley, and B. Descomps. Antiandro-genic effects of Permixon in vitro studies. Acta Urol Ital 1987 1(4) 23. Ragab, A., ]. Ragab, A. Delhon, et al. Effects of Permixon on phospholipase A2 activity and on arachidonic acid... 

A detailed analysis of the effect of mixed monolayers of 15 and DMPC on the activity of phospholipase A2 was reported by Grainger et al. [53]. Monolayers composed of different ratios of DMPC and either 15 or primarily poly 5 were characterized by Langmuir isotherms and isobars. The phospholipse-A2-mediated hydrolysis of selected monolayer compositions was usefully employed to ascertain the effectiveness of the enzyme. Both 15 and polyl5 were resistant to hydrolysis. The DMPC hydrolysis was sensitive to its molecular environment in a manner that suggests the phase separation of the polyl5 from DMPC. Phospholipase A2 activity is known to be sensitive to the concentration of the hydrolytic products, i.e. the fatty acid and lysophospholipid. The effect of these reaction products of the activity of phospholipase A2 on mixed monolayers of nonpolymerizable lipids is the subject of a series of interesting studies which are beyond the scope of this review. Ahlers et al. reviewed some of this research [54],... 

Corticosteroids block all the known pathways of eicosanoid synthesis, perhaps in part by stimulating the synthesis of several inhibitory proteins collectively called annexins or lipocortins. They inhibit phospholipase A2 activity, probably by interfering with... 

Bianco, I. D., Balsinde, J., Beltramo, D. M., Castagna, L. F., Landa, C. A., and Dennis, E. A. (2000). Chitosan-induced phospholipase A2 activation and arachidonic acid mobilization in P388D, macrophages. FEBS Lett. 466, 292-294. 

Farooqui A. A., Ong W. Y., and Horrocks L. A. (2006). Inhibitors of brain phospholipase A2 activity Their neuiopharmacologic effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol. Rev. 58 591-620. 

Thwin M. M., Ong W. Y., Fong C. W., Sato K., Kodama K., Farooqui A. A., and Gopalakrishnakone P. (2003). Secretory phospholipase A2 activity in the normal and kainate injected rat brain, and inhibition by a peptide derived from python serum. Exp. Brain Res. 150 427-433. 

Yedgar S., Cohen Y., and Shoseyov D. (2006). Control of phospholipase A2 activities for the treatment of inflammatory conditions. Biochim. Biophys. Acta 1761 1373-1382. 

Rigoni M, Schiavo G, Weston AE, Caccin P, AUegrini F et al. (2004) Snake presynaptic neurotoxins with phospholipase a2 activity induce punctate swellings of neurites and exocytosis of synaptic vesicles. J Cell Sd 117 3561-70... 

A10. Aufenanger, J., Samman, M., Quintel, M., Fassbender, K., Zimmer, W., and Bertsch, T., Pancreatic phospholipase A2 activity in acute pancreatitis A prognostic marker for early identification of patients at risk. Clin. Chem. Lab. Med. 401, 293-297 (2002). 

LP Vernon, JD Bell. Membrane structure, toxins and phospholipase A2 activity. Pharmacol Ther 54 269-295, 1992. 

AA Farooqui, ML Litsky, T Farooqui, LA Horrocks. Inhibitors of intracellular phospholipase A2 activity their neurochemical effects and therapeutical importance for neurological disorders. Brain Res Bulletin 49 139-153, 1999. 

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