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  • Translocation of calcium-free , response to an enigma

    images28Eicosanoids, proinflammatory compounds with high activity, including prostaglandins, leukotrienes, lipoxins, and in general all oxygenated metabolites of arachidonic acid. In cells, the polyunsaturated fatty acid is usually found esterified to membrane phospholipids. To join the synthesis of eicosanoids release is needed, what is responsible for a group of phospholipases. One of these key biosynthetic process involved in inflammation, cytosolic phospholipase (cPLA2α), which generates free arachidonic acid from membrane phospholipids. In fact, participating in the first stage regulator in the cascade of eicosanoid synthesis.

    This enzyme, which is translocated to the perinuclear membranes shortly after its activation, is unique within the phospholipase A2, due to their specificity for arachidonic acid bound to phospholipids, and calcium and its regulation by phosphorylation.
    Its action is controlled by the increased availability of intracellular calcium, but also catalyzes the hydrolysis of membrane phospholipids in response to stimuli (bacterial lipopolysaccharide, UV radiation, phorbol esters or okadaic acid) that do not mobilize intracellular calcium. The way how the cPLA2α interacts with membranes under conditions in which there is no increase of this ion remained unresolved.

    The authors of this work performed at the Institute of Molecular Biology and Genetics Valladolid CSIC are interested in the design and testing of biological molecules antifosfolipasa A2 activity to assess their potential anti-inflammatory. In his article describing the translocation of the cPLA2α to perinuclear membranes of intact cells by phosphatidylinositol 4,5-bisphosphate, which in turn does depend on peak intracellular calcium concentration. This facilitates polyphosphoinositides anchoring enzyme allows these membranes and interact properly with its phospholipid substrate to release arachidonic acid and ease inflammation.

    Published on August 15, 2012 · Filed under: Bioscience; Tagged as: , , , ,
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