Abstract
Phospholipase A2s (PLA2s) comprises a growing family of enzymes that hydrolyze membrane glycerophospholipids at the sn-2 position, generating free fatty acids containing arachidonic acid (AA) and lysophospholipids. The released AA is converted to prostaglandins (PGs) and leukotrienes by cyclooxygenases (COXs) and 5lipoxygenases (5-LOX), respectively. Lysophospholipids themselves often act as lipid mediators and are also metabolized to other bioactive lipids, such as platelet-activating factor. To date, more than ten PLA2 1 and two COX2 isozymes have been identified in mammals. Type IIA secretory PLA2 (sPLA2-IIA) is a 14-kDa PLA2 that requires millimolar levels of calcium for its activation and is induced by various stimuli such as proinflammatory cytokines and endotoxin in many cell types3’6. sPLA2-IIA is referred to as the inflammatory-type PLA2, since it is highly expressed in the plasma and synovial fluids of patients with various inflammatory diseases such as rheumatoid arthritis, pancreatitis, Crohn’s disease, and endotoxic shock6 as well as various cancers’. Cytosolic PLA2 (cPLA2: type IV) is an 85 kDa PLA2 that is constitutively expressed in various cells and tissues8’9. This enzyme preferentially hydrolyzes AA from membrane phospholipids and requires micromolar calcium for its activation. Both the phosphorylation and calcium-dependent translocation of cPLA2 to the membranes are essential for its activation10. Current evidence suggests that the existence of two kinetically distinct PG-biosynthetic responses, the immediate and delayed phases, implies the recruitment of different sets of biosynthetic enzymes to this pathway11.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
E. A. Dennis, The growing phospholipase A2 superfamily of signal transduction enzymes, Trends Biochem. Sci. 22, 1 (1997)
W. L. Smith, R. M. Garavito, and D. L. DeWitt, Prostaglandin endoperoxide H synthases (cyclooxygenases)1 and -2, J. Biol. Chem. 271, 33157 (1996)
H. Kuwata, Y. Nakatani, M. Murakami, and I. Kudo, Cytosolic phospholipase A2 is required for cytokine-induced expression of type HA secretory phospholipase A2 that mediates optimal cyclooxygenase-2dependent delayed prostaglandin E2 generation in rat 3Y1 fibroblasts, J. Biol. Chem. 273, 1733 (1998)
H. Naraba, M. Murakami, H. Matsumoto, S. Shimbara, A. Ueno, I. Kudo, and S. Oh-ishi, Segregated coupling of phospholipases A2, cyclooxygenases, and terminal prostanoid synthases in different phases of prostanoid biosynthesis in rat peritoneal macrophages, J. Immunol. 160, 2974 (1998)
M. Murakami, H. Kuwata, Y. Amakasu, S. Shimbara, Y. Nakatani, G. Atsumi, and I. Kudo, Prostaglandin E, amplifies cytosolic phospholipase A2- and cyclooxygenase-2-dependent delayed prostaglandin E2 generation in mouse osteoblastic cells: enhancement by secretory phospholipase A2, J. Biol. Chem. 272, 19891 (1997)
M. Murakami, Y. Nakatani, G. Atsumi, K. Inoue, and I. Kudo, Regulatory functions of phospholipase A2, Crit. Rev. Immunol. 17, 225 (1997)
T. Abe, K. Sakamoto, H. Kamohara, Y. Hirano, N. Kuwahara, and M. Ogawa, Group II phospholipase A2 is increased in peritoneal and pleural effusions in patients with various types of cancer, Int. J. Cancer. 74, 245 (1997)
I. Kudo, M. Murakami, S. Hara, and K. Inoue, Mammalian non-pancreatic phospholipases A2, Biochim. Biophys. Acta 1170, 217 (1993)
J. D. Clark, L. L. Lin, R. W. Kriz, C. S. Ramesha, L. A. Sultzman, A. Y. Lin, N. Milona, J. L. Knopf, A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2)-dependent translocation domain with homology to PKC and GAP, Cell 65, 1043 (1991)
L. L. Lin, A. Y. Lin, and J. L. Knopf, Cytosolic phospholipase A2 is coupled to hormonally regulated release of arachidonic acid, Proc. Natl. Acad. Sci. U. S. A. 89, 6147 (1992)
K. Tada, M. Murakami, T. Kambe, I. Kudo, Induction of cyclooxygenase-2 by secretory phospholipases A2 in nerve growth factor-stimulated rat serosal mast cells is facilitated by interaction with fibroblasts and mediated by a mechanism independent of their enzymatic functions, J. Immunol. 161, 5008 (1998)
M. Murakami, T. Kambe, S. Shimbara, I. Kudo, Functional coupling between various phospholipase A2s and cyclooxygenases in immediate and delayed prostanoid biosynthetic pathways, J. Biol. Chem. 274, 3103 (1999)
H. Shinohara, M. A. Balboa, C. A. Johnson, J. Balsinde, E. A. Dennis, Regulation of delayed prostaglandin production in activated P388D, macrophages by group IV cytosolic and group V secretory phospholipase A2s, J. Biol. Chem. 274, 12263 (1999)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer Science+Business Media New York
About this chapter
Cite this chapter
Kuwata, H., Yamamoto, S., Nakatani, Y., Murakami, M., Kudo, I. (2002). Type IIA Secretory PLA2-Mediated Delayed PGE2 Biosynthesis is Regulated by the Products of the Cytosolic PLA2 . In: Honn, K.V., Marnett, L.J., Nigam, S., Dennis, E., Serhan, C. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5. Advances in Experimental Medicine and Biology, vol 507. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0193-0_2
Download citation
DOI: https://doi.org/10.1007/978-1-4615-0193-0_2
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4960-0
Online ISBN: 978-1-4615-0193-0
eBook Packages: Springer Book Archive