Functional coupling between Phospholipase a2s and cyclooxygenases in immediate and delayed prostanoid biosynthetic pathways
Phospholipase A2 (PLA2) and cyclooxygenase (COX) represent the two crucial rate-limiting steps for the PG-biosynthetic pathway. To date, more than ten PLA2 and two COX isozymes have been identified in mammals. 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 pathway. A rapidly expanding body of evidence suggests that the two COXs, the constitutive COX-1 and inducible COX-2, play distinct roles in regulating AA metabolism. Generally, utilization of COX-1 is observed during the early phase of PG biosynthesis occurring within several minutes of stimulation, whereas COX-2-dependent PG generation proceeds over several hours in parallel with the induction of COX-2 expression.l-4 However, whether distinct PLA2s are utilized selectively in the different PG-biosynthetic phases and couple specifically with each COX isozyme is controversial.
KeywordsHeparan Sulfate Proteoglycan Functional Coupling Arachidonic Acid Release Cytosolic Phospholipase Secretory Phospholipase
Unable to display preview. Download preview PDF.
- 3.M. Murakami, H. Kuwata, Y. Amakasu, S. Shimbara, Y. Nakatani, G. Atsumi, and I. Kudo, Prostaglandin E2 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)PubMedCrossRefGoogle Scholar
- 4.H. Kuwata, Y. Nakatani, M. Murakami, and I. Kudo, Cytosolic phospholipase A2 is required for cytokine-induced expression of type IIA secretory phospholipase A2 that mediates optimal cyclooxygenase-2dependent delayed prostaglandin E2 generation in rat 3Y1 fibroblasts, J. Biol. Chem. 273: 1733 (1998)PubMedCrossRefGoogle Scholar
- 5.M. Murakami, S. Shimbara, T. Kambe, H. Kuwata, M. V. Winstead, J. A. Tischfield, and I. Kudo, The functions of five distinct mammalian phospholipase A2s in regulating arachidonic acid release: type IIA and type V secretory phospholipase A2s are functionally redundant and act in concert with cytosolic phospholipase A2, J. Biol. Chem. 273: 14411 (1998)PubMedCrossRefGoogle Scholar
- 7.M. Murakami, T. Kambe, S. Shimbara, K. Higashino, K. Hanasaki, H. Arita, M. Horiguchi, M. Arita, H. Arai, K. Inoue, and I. Kudo, Different functional aspects of the group II subfamily (types IIA and V) and type X secretory phospholipase A2s in regulating arachidonic acid release and prostaglandin generation: implication of cyclooxygenase-2 induction and phospholipid scramblase-mediated cellular membrane perturbation, J. Biol. Chem. 274: 31435 (1999)PubMedCrossRefGoogle Scholar
- 8.M. Murakami, T. Kambe, S. Shimbara, S. Yamamoto, H. Kuwata, and I. Kudo, Functional association of type IIA secretory phospholipase A2 with the glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan in the cyclooxygenase-2-mediated delayed prostanoid biosynthetic pathway, J. Biol. Chem. 274: 29927 (1999)PubMedCrossRefGoogle Scholar