Abstract
Human cytosolic phospholipase A2 (cPLA2, 85 kDa) appears to be pharmacologically distinct from human secretory phospholipase A2 (sPLA2, 14 kDa). Marine natural products and PLA2 substrate and product analogs were potent inhibitors of human recombinant sPLA2 (r-sPLA2), whereas these compounds stimulated, weakly inhibited, or had no effect on cPLA2 activity from the human monocytic cell line U937. In contrast, within a series of seven reported calmodulin (CaM) antagonists tested, significant correlations among the rank order of potencies of these compounds as inhibitors of cPLA2, r-sPLA2, and a CaM-dependent phosphodiesterase were observed. The correlated inhibitory effects of the hydrophobic CaM antagonists on cPLA2 and sPLA2 may reflect a common feature (possibly a hydrophobic domain) shared by these two types of enzymes.
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J. D. Clark, N. Milona and J. L. Knopf,Purification of a 110-kilodalton cytosolic phospholipase A 2 from the human monocytic cell line U937. Proc. Natl. Acad. Sci.87, 7708–7712 (1990).
R. M. Kramer, E. F. Roberts, J. Manetta and J. E. Putnam,The Ca 2+-sensitive cytosolic phospholipase A 2 is a 100-kDa protein in human monoblast U937 cells. J. Biol. Chem.266, 5268–5272 (1991).
M. T. Withnall, T. J. Brown and B. K. Diocee,Calcium regulation of phospholipase A 2 is independent of calmodulin. Biochem. Biophys. Res. Commun.121, 507–513 (1984).
H. Krause, P. Dieter, A. Schulze-Specking, A. Ballhorn, E. Ferber and K. Decker,Synergistic effect of magnesium and calcium ions in the activation of phospholipase A 2 of liver macrophages. Biochem. Biophys. Res. Commun.175, 532–536 (1991).
K. I. Hulkower, W. C. Hope, T. Chen, C. M. Anderson, J. W. Coffey and D. M. Morgan,Interleukin-1β stimulates cytosolic phospholipase A 2 in rheumatoid synovial fibroblasts. Biochem. Biophys. Res. Commun.184, 712–718 (1992).
W. C. Hope, B. J. Patel, C. Fiedler-Nagy and B. H. Wittreich,Retinoids inhibit phospholipase A 2 in human synovial fluid and arachidonic acid release from rat peritoneal macrophages. Inflammation14, 543–559 (1990).
W. Levin, R. F. Daniel, C. R. Stoner, T. J. Stoller, J. A. W. Swanson, Y. M. Angelillo, P. C. Familletti and R. M. Crowl,Purification of recombinant human secretory phospholipase A 2 (group II) produced in long-term immobilized cell culture. Protein Expression and Purification3, 27–35 (1992).
A. F. Welton, W. C. Hope and G. Wiggan,Studies on the ability of calmodulin antagonists to inhibit, a soluble phospholipase A 2 from snake venom InAdv. Cyclic Nucleotide Protein Phosphorylation Res., vol. 17A (Ed. P. Greengard), p. 76, Raven Press, New York 1983.
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Hope, W.C., Chen, T. & Morgan, D.W. Secretory phospholipase A2 inhibitors and calmodulin antagonists as inhibitors of cytosolic phospholipase A2 . Agents and Actions 39 (Suppl 1), C39–C42 (1993). https://doi.org/10.1007/BF01972714
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DOI: https://doi.org/10.1007/BF01972714