- 作者: Chia-Yu Chang; Kathryn R. Farrell; Rodney C. Baker
- 作者服務機構: Department of Pharmacology and Toxicology, University Mississippi Medical Center, Jackson, Miss., USA
- 中文摘要: --
- 英文摘要: The synthesis of inflammation mediators produced fromarachidonic acid is regulated primarily by the cellularconcentration of free arachidonic acid. Since intracellulararachidonic acid is almost totally present as phospholip-id esters, the concentration of intracellular arachidonicacid is primarily dependent on the balance between therelease of arachidonic acid from membrane phospholip-ids and the uptake of arachidonic acid into membranephospholipids. Cytosolic phospholipase A2 is a calcium-dependent enzyme that catalyzes the stimulus-coupledhydrolysis of arachidonic acid from membrane phospho-lipids. Following exposure of macrophages to variousforeign or endogenous stimulants, cytosolic phospholi-pase A2 is activated. Treatment with these compoundsmay also stimulate phospholipase D activity, and, in thepresence of ethanol, phospholipase D catalyzes the syn-thesis of phosphatidylethanol. A cell-free system wasused to evaluate the effect of phosphatidylethanol oncytosolic phospholipase A2 activity. Phosphatidylethanol(0.5 uM) added to 1-stearoyl-2-[3H]-arachidonoyl-sn-gly-cero-3-phosphocholine vesicles stimulated cytosolicphospholipase A2 activity. However, high concentrations(20-100 uM) of phosphatidylethanol inhibited cytosolicphospholipase A2 activity. Phosphatidic acid, the normalphospholipase D product, also stimulated cytosolicphospholipase A2 activity at 0.5 uM, but had an inhibitoryeffect on cytosolic phospholipase A2 activity at concen-trations of 50 and 100 uM. Ethanol (20-200 mM), the pre-cursor of phosphatidylethanol, added directly to the as-say did not alter cytosolic phospholipase A2 activity.These results suggest that phosphatidylethanol altersthe physical properties of the substrate, and at lowerconcentrations of anionic phospholipids the substrate ismore susceptible to hydrolysis. However, at high con-centrations, phosphatidylethanol either reverses the al-terations in physical properties of the substrate or phos-phatidylethanol may be competing as the substrate.Both interactions may result in lower cytosolic phospho-lipase A2 activity.
- 中文關鍵字: --
- 英文關鍵字: --