Phospholipase A2 activating protein (PLAA) is required for 1α,25(OH)2D3 signaling in growth plate chondrocytes

摘要: Phospholipase A 2 (PLA ) is pivotal in the rapid membrane-mediated actions of 1,25-dihydroxyvitamin D3 [1α,25(OH) D 3 ]. Microarray analysis indicated that PLA activating protein (PLAA) mRNA upregulated 6-fold before rat growth plate cells exhibit 1α,25(OH) -dependent kinase C (PKC) increases, suggesting it plays an important role 's mechanism action. PLAA was confirmed -responsive zone (prehypertrophic and upper hypertrophic cell zones) chondrocytes by RT-PCR Northern blot vitro situ hybridization vivo. shown Western immunohistochemistry. PLAAs signaling evaluated cultures using peptide. Arachidonic acid release increased as -specific activity plasma membranes matrix vesicles. PKCa, but not PKCβ, PKCe, or PKCζ, increased. effect comparable to 1 α,25(OH) additive with . inhibitors quinacrine AACOCF3, cyclooxygenase inhibitor indomethacin blocked peptide on PKC, indicating arachidonic its metabolites were involved. This exogenous acid. Prostaglandin acted via EP1 based inhibition SC19220 EP2 since AH6809 had no effect. Like , also phospholipase C-specific beta-1 beta-3 isoforms, delta-1 gamma-1; lysophospholipid decreased [ H]-thymidine incorporation 50% decrease caused In contrast, alkaline phosphatase-specific proteoglycan production a manner similar indicates specific activator chondrocytes, suggests mediates membrane thereby modulating physiological response.