Structural and Functional Properties of Mammalian Group III Cytosolic Phospholipases A2
Phospholipases A2, enzymes which hydrolyze the sn-2 fatty acyl ester bond of phosphoglycerides, are found in all mammalian cells and tissues1. They have been subdivided into two groups: group I enzymes are derived from proenzymes and secreted. These extracellular enzymes have been characterized in great detail functionally and structurally, the best known mammalian enzyme being the pancreatic phospholipase A2. Group II enzymes are structurally related to the group I enzymes. They have the same molecular weight of about 12 to 18 kD and show a high degree of sequence homology, but also typical differences such as a lacking cysteine residue in position 11, which is typical for group I enzymes. Group II phospholipases A2 are found intracellularly, often membrane bound, and are secreted upon activation of the cells. Functionally they seem to play an important role in inflammations and other disease states2,3. It has now become evident that there is a third group of calcium-dependent phospholipases A2 distinct from the ones mentioned above. These enzymes are rather labile when purified and therefore not yet well characterized. They have been described in most detail in platelets, mesangial cells, macrophages and monocytic cell lines. The present paper will discuss some of the properties of these group III enzymes (cytosolic phospholipases A2) and will focus on the phospholipase A2 from the monocytic cell line THP1.
KeywordsArachidonic Acid U937 Cell THP1 Cell Membrane Association Monocytic Cell Line
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- 01.H. van den Bosch, Intracellular phospholipases A, Bioch. Biophys. Acta. 604: 191 (1980)Google Scholar
- 02.E. Kaiser, P. Chiba, and K. Zaky, Phospholipases in Biology and Medicine, Clin. Biochem. 23: 349 (1990)Google Scholar
- 03.W. Pruzsanski and P. Vadas, Phospholipase A2 - a mediator between proximal and distal effectors of inflammation, Immunol. Today. 12: 143 (1991)Google Scholar
- 05.J.H. Gronich, J.V. Bonventre, and R.A. Nemenoff, Purification of a high-molecular-mass form of phospholipase A2 from rat kidney activated at physiological calcium concentrations, Biochem. J. 271: 37 (1990)Google Scholar
- 15.B. Rothhut, C. Cornera, B. Prieur, M. Errasfa, G. Minassian, and F. Russo-Marie, Purification and characterization of a 32-kDa phospholipase A2 inhibitory protein (lipocortin) from human peripheral blood mononuclear cells, FEBS 219: 169 (1987)Google Scholar
- 16.I. Flesch, B. Schmidt, and E. Ferber, Acylchain Specificity and Kinetic Properties of Phospholipase Al and A2 of Bone Marrow-derived Macrophages, Z. Naturforsch. 40c: 356 (1985)Google Scholar
- 18.M. Goppelt-Struebe, R. Hass, and W. Rehfeldt, Characterization of phospholipase A2 in monocytic cell lines; functional and biochemical aspects of membrane association. Biochem. J. in press (1991)Google Scholar
- 25.F.F. Davidson and E.A. Dennis, Biological relevance of lipocortins and related proteins as inhibitors of phospholipase A2, Biochem. Pharm. 38: 3645 (1989)Google Scholar
- C.A. Rouzer, A.W. Ford-Hutchinson, H.E. Morton and J.W. Gillard, MK886, a Potent and Specific Leukotriene Biosynthesis Inhibitor Blocks and Reverses the Membrane Association of 5Lipoxygenase in Ionophore-challenged Leukocytes, J. Biol. Chem., 265:1436 (1990)Google Scholar
- 33.J.N. Fain, M.A. Wallace, and R.J.J. Wojcikiewicz, Evidence for involvement of guanine nucleotide-binding regulatory proteins in the activation of phospholipase by hormones. FASEB 2: 2569 (1988)Google Scholar