TY - JOUR
T1 - Fatty acid binding proteins stabilize leukotriene A4
T2 - Competition with arachidonic acid but not other lipoxygenase products
AU - Dickinson Zimmer, Jennifer S.
AU - Dyckes, Douglas F.
AU - Bernlohr, David A.
AU - Murphy, Robert C.
PY - 2004/11
Y1 - 2004/11
N2 - Leukotriene A4 (LTA4) 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 s at 37°C and ∼40 s at 4°C. 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 LTA 4 to ∼20 min at 4°C. Five FABPs (adipocyte FABP, intestinal FABP, E-FABP, heart/muscle FABP, and liver FABP) have now been examined and also found to increase the half-life of LTA4 at 4°C to ∼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 at concentrations 3-fold higher than LTA4.
AB - Leukotriene A4 (LTA4) 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 s at 37°C and ∼40 s at 4°C. 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 LTA 4 to ∼20 min at 4°C. Five FABPs (adipocyte FABP, intestinal FABP, E-FABP, heart/muscle FABP, and liver FABP) have now been examined and also found to increase the half-life of LTA4 at 4°C to ∼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 at concentrations 3-fold higher than LTA4.
KW - Half-life
KW - Leukotriene biosynthesis
KW - Transcellular biosynthesis
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U2 - 10.1194/jlr.M400240-JLR200
DO - 10.1194/jlr.M400240-JLR200
M3 - Article
C2 - 15342681
AN - SCOPUS:21644440188
SN - 0022-2275
VL - 45
SP - 2138
EP - 2144
JO - Journal of lipid research
JF - Journal of lipid research
IS - 11
ER -