Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: C44C10 .12
 59,182 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elicited rat peritoneal mononuclear cells converted arachidonic acid to a new dihydroxy acid, 5(S), 15(S)-dihydroxy-6,13-trans-8,11-cis-eicosatetraenoic acid (5,15-DiHETE). In this system, the amount of 5,15-DiHETE formed was about 20% that of leukotriene B4. The structure of the compound was determined by ultraviolet and mass spectrometric analysis, and comparison to a reference compound prepared by incubation of synthetic 5(R,S)-hydroxy- or hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5(R,S)-HETE or HPETE) with soybean lipoxygenase (linoleate:oxygen oxidoreductase, EC 1.13.11.12). Cell incubations performed under an atmosphere of 18O2 demonstrated that both hydroxyl groups in the cell product derived from molecular oxygen and that the oxygen atoms were from different oxygen molecules. Steric analysis indicated that each hydroxyl group had the S-configuration. The structural data thus indicate that 5,15-DiHETE is formed by an enzymatic double oxygenation of arachidonic acid catalyzed by both C-5 and C-15 lipoxygenases. Incubations with with [3H 8]5 (S)-HETE and [3H8]15(S)-HETE revealed that both compounds could be converted to the product. When [3H8]5(S), 15(S)-DiHPETE was added to cells, the majority of the substrate was reduced to 5,15-DiHETE. Leukocytes obtained from three human donors with peripheral blood eosinophilia also synthesized 5,15-DiHETE. Formation of the compound occurred in both eosinophils and neutrophils from these donors.
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PMID:Formation of a novel dihydroxy acid from arachidonic acid by lipoxygenase-catalyzed double oxygenation in rat mononuclear cells and human leukocytes. 680 63

Induction of epidermal ornithine decarboxylase (ODC) by a topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, was inhibited by treatment of mouse skin with phenidone (3-90 mumol/mouse), nordihydroguaiaretic acid (30 mumol/mouse) or 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW 755C, 30 mumol/mouse), which are well-known lipoxygenase inhibitors. Phenidone and BW 755C are also to be cyclooxygenase inhibitors. Inhibition of TPA-induced ODC by indomethacin (1.12 mumol/mouse), a selective cyclooxygenase inhibitor, was counteracted by prostaglandin E2 (PGE2) (140 nmol/mouse). This counteracting effect of PGE2 was reversed by the treatment of mice with nordihydroguaiaretic acid (30 mumol/mouse) or phenidone (30 mumol/mouse). ODC activity which was suppressed by nordihydroguaiaretic acid or phenidone at a dose of 180 mumol/mouse was not further inhibited by indomethacin (1.12 mumol/mouse). In addition, the counteracting action of PGE2 (140 nmol/mouse) was not observed in mice treated with nordihydroguaiaretic acid or phenidone at a dose of 180 mumol/mouse. Thus, the suppressive effect of nordihydroguaiaretic acid or phenidone on the ODC induction by TPA would be due to the inhibition of lipoxygenase. The above findings strongly suggest that not only cyclooxygenase product (i.e., PGE2) but also lipoxygenase product(s) are involved in the mechanism of ODC induction in mouse epidermis, and a lack of either cyclooxygenase product or lipoxygenase product(s) causes a failure of ODC induction by TPA.
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PMID:Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity by lipoxygenase inhibitors: possible role of product(s) of lipoxygenase pathway. 681 41

The aim of this investigation was to determine whether chain-breaking antioxidants able to prevent lipid peroxidation can inhibit lipoxygenase-1 (EC 1.13.11.12). Therefore, the effects of ascorbic acid, 6-palmitoylascorbic acid and trolox on the enzyme activity were analyzed by means of Lineweaver-Burk double reciprocal plots and Yoshino's graphical method. The effect of these compounds on the formation of free radicals during lipoxygenase-1 reaction was investigated as well, by monitoring the enzymic formation of oxodienes. We present evidence that the chain-breaking antioxidants ascorbic acid, 6-palmitoylascorbic acid and trolox inhibit soybean lipoxygenase-1 in the micromolar concentration range (Ki 27, 3 and 18 microM, respectively). The inhibition is competitive, complete and reversible. All three compounds trap the free radicals formed during the lipoxygenase-catalyzed reaction, which might substantially contribute to their inhibitory ability. These findings can have physiological significance in the light of the lipoxygenase involvement in biomembrane remodelling.
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PMID:Inhibition of soybean lipoxygenase-1 by chain-breaking antioxidants. 776 Jun 88

Soybean lipoxygenase (LOX; EC 1.12.11.12) catalyzes the oxygenation of polyunsaturated fatty acids, acylglycerols and phosphoglycerols, producing a regio- and enantiospecific hydroperoxide product. The goal of this work was to measure the relative rate of LOX-catalyzed oxidation of mixtures of lipids containing linoleate, using high-performance liquid chromatography (HPLC) and a light-scattering detector (LSD). Previous literature suggested that reversed-phase HPLC with silica-based columns could be used for the separation of individual fatty acids, acylglycerols, phosphoglycerides and their oxidation products. However, these columns produced ineffective separations of phosphoglycerides unless choline chloride and a strong base, such as KOH, are present in the mobile phase. Such modifiers precluded the use of the LSD. It was found that a reversed-phase column based upon an organic polymer support, rather than on silica, was able to separate these mixtures with a ternary solvent gradient of methanol/water/acetonitrile without the need for the addition of modifiers. The oxidation time course of a mixture of linoleic acid, trilinolein and 1-linoleoyl-2-stearoyl-sn-glycero-3-phosphocholine was followed using the developed HPLC method. The results showed that trilinolein and phosphatidylcholine reacted at one-tenth the rate of linoleic acid. The diacylglycerol, 1,3-dilinolein, was oxidized at a rate that was approximately 40% that of linoleic acid, with the formation of mono- and dihydroperoxides as well as other unidentified products.
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PMID:Analysis of lipoxygenase kinetics by high-performance liquid chromatography with a polymer column. 776 68

ESWL is a safe and effective first-line treatment for urinary tract stone disease (UTSD) in children. The major complications arising from this procedure were upper urinary tract obstruction and ureteral colic. It was shown that prostaglandin synthetase inhibitors were effective in the treatment of urethral colic. The aim of this study was to measure urinary and plasma prostaglandin E2 (PGE2)- and leukotriene C4 (LTC4)-like activity in the patients who underwent ESWL before and after the treatment and investigate the role of cyclooxygenase (CO) and lipoxygenase (LO) products in early and late complications of ESWL. Urinary PGE2-like activity were increased 1 h after ESWL. (1.19 +/- 0.12 vs 1.59 +/- 0.15 g/ml, p < 0.02). The plasma values were decreased significantly after the treatment (16.7 +/- 1.7 vs 11.6 +/- 1.2 g/ml, p < 0.005). Urinary and plasma LTC4-like activities were found to be significantly decreased in the post-ESWL samples (0.58 +/- 0.006 vs 0.39 +/- 0.04, p < 0.002; 8.6 +/- 0.9 vs 4.2 +/- 0.6, p < 0.001, respectively). In conclusion, ESWL may stimulate the release of PG from the urinary tract resulting in increased peristaltism and the passage of stone fragments into the bladder. As this group of drugs has also nephrotoxic effects, they can be given prophylactically only to selected patients.
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PMID:The role of prostanoids in the complications of extracorporeal shock wave lithotripsy (ESWL) in children. 784 11

A lipoxygenase (EC 1.13.11.12) activity on the plasmalemma of sunflower (Helianthus annuus L.) protoplasts and its possible modulation by regulatory molecules were investigated. The activity was followed as both linolenic acid-dependent conjugated diene formation and oxygen uptake. Protoplasts exhibited a lipoxygenase activity inhibited by propyl gallate, salicylhydroxamic acid and butylated hydroxytoluene, and stimulated by the addition of CaCl2, H2O2 and ATP. The stimulation by CaCl2 and H2O2 was evident up to 1.5 mM and 5 nM, respectively. Higher concentrations of H2O2 caused a lower extent of stimulation and then became inhibitory. The stimulatory effect of CaCl2 was prevented by chelators (EGTA or EDTA), a Ca2+ channel blocker (gadolinium oxide) or a Ca2+ ionophore (A23187). Negligible lipoxygenase was released from protoplasts after 6 h incubation in 3.6 mM MES-Tris (pH 5.6), 0.5 M glycine betaine and 1 mM CaCl2, whereas mechanical disruption of cell integrity, liberating soluble lipoxygenase, strongly increased such an activity. However, microsomal membranes obtained from hypocotyls still retained a part of this activity which was also recovered in a highly purified plasma membrane preparation.
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PMID:Lipoxygenase activity on the plasmalemma of sunflower protoplasts and its modulation. 789 38

Lipoxygenase (LOX) (EC 1.13.11.12) oxidized a wide range of phenothiazine (Pt) tranquillizers to their corresponding radical cations in the presence of H2O2 by means of an enzymatic chemical second-order mechanism with substrate regeneration similar to that of horseradish peroxidase. The optimum pH of LOX for this hydroperoxidase activity was in the acid range (pH 3.0-4.0), as has been shown for other Pt oxidizing systems, such as peroxidase/H2O2 and haemoglobin. LOX showed Michaelis constants for Pt ranging from 1.4 to 8.5 mM and which, in some cases, e.g. trifluoperazine, displayed substrate inhibition. By contrast, it had a high affinity for H2O2 in the microM to mM range. A new, previously undescribed plot, which relates the enzymatic affinity and the apparent second-order decay of the cation radical, was developed to study the influence of the 2- and 10-substituents in the Pt ring. The implications of this new plot and the LOX-mediated Pt oxidation are also discussed.
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PMID:Enzymatic oxidation of phenothiazines by lipoxygenase/H2O2 system. 803 16

The reticulocyte 15-lipoxygenase (linoleate:oxygen oxidoreductase, EC 1.13.11.12) is implicated in oxidative damage to reticulocyte mitochondria before their elimination by degradation during maturation to the erythrocyte. A proportion of the 15-lipoxygenase sediments with the mitochondrial-rich stromal fraction of density-gradient-fractionated rabbit reticulocytes suggesting a physical association with mitochondria before their elimination. Ca2+ promotes binding of reticulocyte 15-lipoxygenase to isolated rat liver and reticulocyte mitochondria and 15-lipoxygenase-mediated lipid peroxidation of mitochondrial lipids and free linoleic acid. Association of reticulocyte 15-lipoxygenase with isolated mitochondria is not simply a consequence of Ca(2+)-induced swelling, but implies that Ca2+ mediates translocation of soluble lipoxygenase to mitochondrial membranes. Therefore, Ca2+ may have an important physiological role in the regulation of 15-lipoxygenase-mediated targeting of reticulocyte mitochondria for degradation.
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PMID:Calcium promotes membrane association of reticulocyte 15-lipoxygenase. 813 44

A regulatory role of endogenously synthesized eicosanoids on the absorption, transmural transport and metabolism of glucose in perfused, isolated loops of jejunum in vitro was investigated using the lipoxygenase/cyclooxygenase inhibitor, nordihydroguaiaretic acid (NDGA). NDGA diminished glucose absorption over the range 100-500 microM: maximal inhibition at 500 microM NDGA was 52 +/- 9 and 64 +/- 9% (mean +/- SE, P < 0.001) for jejuna from fed rats and rats maintained on glucose water for 48 hr, respectively. In each instance, transmural transport was effectively abolished. The vectorial disposition of lactate release was also changed such that the ratio of luminal to serosal production was increased from 0.19 +/- 0.02 to 1.72 +/- 0.12 (P < 0.001) in fed rats, indicating inhibition of the Na+ pump. NDGA inhibited (Na(+)+K+)-ATPase activity in whole mucosal homogenates with a concentration dependence similar to that observed for glucose absorption. However, NDGA also inhibited Mg(2+)-ATPase activity in whole homogenates and purified rabbit skeletal muscle phosphofructokinase under the same conditions. The results are discussed in terms of the dissipation of the transmembrane Na+ gradient via direct inhibition of the (Na(+)+K+)-ATPase by NDGA. Inhibition of the ATPase precludes the use of NDGA as a suitable drug with which to investigate the role of endogenously synthesized eicosanoids in the regulation of intestinal function.
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PMID:Effect of nordihydroguaiaretic acid on glucose absorption, metabolism and (Na(+)+K+)-ATPase activity in rat jejunum. 838 12

1. Trout bradykinin ([Arg0, Trp5, Leu8]-bradykinin; trout BK), recently isolated from kallikrein-treated trout plasma, produced sustained and concentration-dependent contractions of isolated longitudinal muscle from rainbow trout stomach (pD2 = 7.01 +/- 0.03) and proximal small intestine (pD2 = 7.37 +/- 0.07). The maximum responses were 85 +/- 2% (stomach) and 101 +/- 35% (intestine) of the corresponding responses to 10(-5) M acetylcholine. Strips of circular smooth muscle from trout stomach and intestine did not contract in response to trout BK. 2. The potency of trout BK on gastric smooth muscle motility was significantly (5 fold; P < 0.01) reduced in the presence of the cyclo-oxygenase inhibitor, indomethacin (10(-5) M) and by 4 fold (P < 0.05) in the presence of the lipoxygenase inhibitor, MK-886 (10(-6) M), but there was no effect on the maximum response. Potency was also significantly reduced in the presence of 10(-6) M methysergide (3 fold; P < 0.02) and 10(-6) M tetrodotoxin (2 fold, P < 0.05) but atropine was without effect. 3. [Tyr0, Trp5, Leu8]-BK was a full agonist but was approximately 50 fold less potent (pD2 = 5.35 +/- 0.08) than trout BK, [Arg0, Trp5, Leu8]des-Arg9-BK was a partial) agonist (pD2 = 6.80 +/- 0.03; 56 +/- 7% of the maximum response to trout BK) but [Trp5, Leu8]-BK, [Trp5,Leu8]-des-Arg9-BK and mammalian BK produced no, or only very weak, contractions of the trout stomach. 4. The mammalian B1 receptor antagonist, [Leu8]des-Arg9-BK was without effect on the response of the trout stomach to trout BK. The potent mammalian B2 receptor antagonist Hoe 140 was a partial agonist (pD2 = 7.44 +/- 0.12; 57 +/- 15% of the maximum response to trout BK). 5. We conclude that the effects of trout BK on the motility of rainbow trout gastric smooth muscle are mediated through interaction with a receptor that has appreciably different ligand-binding properties than the mammalian B1 and B2 receptor subtypes. An involvement of arachidonic acid metabolites and 5-hydroxytryptaminergic nerves in the mechanism of action of the peptide is suggested.
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PMID:Effects of trout bradykinin on the motility of the trout stomach and intestine: evidence for a receptor distinct from mammalian B1 and B2 subtypes. 917 96


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