Fatty acid-binding proteins: stabilization of leukotriene A4 and competition with arachidonic acid

Jennifer S. Dickinson Zimmer, Douglas F. Dyckes, David A. Bernlohr, and Robert C. Murphy

Pharmacology Dept., University of Colorado Health Sciences Center, Aurora, CO 80045

Corresponding Author: robert.murphy{at}uchsc.edu

Leukotriene A4 is a chemically reactive conjugated triene epoxide product derived from 5-lipoxygenase oxygenation of arachidonic acid. At physiological pH, this reactive compound has a half-life of less than 3 sec at 37ºC and approximately 40 sec at 4ºC. Regardless of this aqueous instability, LTA4 is an intermediate in the formation of biologically active leukotrienes, which can be formed through either intracellular or transcellular biosynthesis. Previously, epithelial fatty acid-binding protein (E-FABP) present in RBL-1 cells was shown to increase the half-life of LTA4 to approximately 20 min at 4ºC. Five fatty acid binding proteins, including A-FABP, I-FABP, E-FABP, H/M FABP, and L-FABP have now been examined and also found to increase the half-life of LTA4 at 4ºC to approximately 20 min with protein present. Stabilization of LTA4 was examined when arachidonic acid was present to compete with LTA4 for the binding site on E-FABP. Arachidonate has an apparent higher affinity for E-FABP than LTA4 and was able to completely block stabilization of the latter. When E-FABP is not saturated with arachidonate, FABP can still stabilize LTA4. Several lipoxygenase products, including 5-hydroxyeicosatetraenoic acid, 5,6-dihydroxyeicosatetraenoic acid, and leukotriene B4 were found to have no effect on the stability of LTA4 induced by E-FABP even when present in concentration 3-fold higher than LTA4.

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