Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differential hybridization was used to isolate genes induced by viroid infection in tomato plants. Four new cDNA clones encoding a peroxidase, a desaturase-like enzyme, a lipoxygenase, and a proteinase inhibitor, were selected and characterized. All of these genes display a characteristic expression pattern, showing constitutive expression in roots of healthy plants and being ectopically activated in aerial tissues upon viroid infection and ethephon treatment. Possible functions for these genes in the viroid-tomato interaction are proposed. The existence of an integrated program that compiles developmental and defense-related responses is also suggested to explain the characteristic expression pattern detected for these genes as well as for other defense-related genes.
Mol Plant Microbe Interact 1996 Jul
PMID:Characterization of defense-related genes ectopically expressed in viroid-infected tomato plants. 867 18

Leukocytes can take part in an inflammatory response in the heart after myocardial infarction or cardio-thoracic surgery. To investigate the injurious mechanism of activated polymorphonuclear leukocytes (PMN), isolated rat hearts were perfused with phorbol 12-myristate 13-acetate (PMA) activated PMN (3 x 10(6)/ml) alone for 10 min, in combination with a mixture of oxygen free radical scavengers (superoxide dismutase+catalase+thiourea) or in combination with ibuprofen (IBU), a cyclooxygenase inhibitor or diethylcarbamazine (DCM), a lipoxygenase inhibitor or BW 755C, a dual inhibitor of cyclooxygenase and lipoxygenase and an oxygen free radical scavenger. After 30 min of recovery, the hearts were perfusion-fixed with glutaraldehyde for electron microscopical examination. Based on examination of 25 micrographs per heart obtained by a random sampling procedure and on morphometric methods, volume fractions (Vv) of mitochondria (mito), altered mitochondria (alt mito), myofilament, and cellular edema were measured as fractions of myocyte volume. The most important finding was that Vv(alt mito/myocyte) was 0.09 +/- 0.16 and 0.02 +/- 0.04 in the hearts receiving PMN+PMA alone and when scavengers were added, respectively, whilst no changes in mitochondrial ultrastructure was observed after addition of IBU, BW 755C or DCM. Vv(mito/myocyte) was for PMN+PMA alone: 0.33 +/- 0.04, +scavengers: 0.29 +/- 0.02 +IBU:0.29 +/- 0.02, +BW 755C: 0.23 +/- 0.03*, +DCM: 0.28 +/- 0.02 (mean +/- S.D., *P < 0.05 compared to PMN+PMA). Capillary wall volume (cap wall) as a fraction of the whole capillary was also quantified. Vv(cap wall/cap) was for PMN+PMA alone: 0.26 +/- 0.06, +scavengers: 0.22 +/- 0.03, +IBU: 0.19 +/- 0.04*, +BW755C: 0.21 +/- 0.03, +DCM: 0.15 +/- 0.04* (*P < 0.05). These results further strengthen the notion that activated PMN are intravascularly active. In addition to exerting a cardiodepressive effect the present study shows that activated PMN can induce structural changes in the heart through the combined action of oxygen free radicals and arachidonic acid metabolites.
J Mol Cell Cardiol 1996 Feb
PMID:Cardiac injury by activated leukocytes: effect of cyclooxygenase and lipoxygenase inhibition evaluated by electron microscopical morphometry. 872 63

We have characterized the binding of Ca2+ and Mg2+ to the anti-inflammatory drug diflunisal in acetonitrile and demonstrated the drug-mediated transport of Ca2+ across the lipid bilayer in unilamellar vesicles made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Fluorescence and difference absorption spectral data show that diflunisal undergoes a significant conformational change on binding Ca2+ and Mg2+ forming, respectively, 1:2 and 1:1 cation:drug complexes with Kd in the low microM range. The kinetics of transport showed that Ca2+ was transported into the vesicle as 1:2 Ca2+:diflunisal sandwich complex. This suggests that the interaction of the drug with the cation in the lipid-mimetic solvent are similar. The biological relevance of the Ca(2+)-binding and translocating abilities of diflunisal is examined in light of the reported ionophoretic properties of several phospholipids as well as cyclooxygenase and lipoxygenase products.
Biochem Mol Biol Int 1996 May
PMID:Ca2+ binding and translocating properties of diflunisal. 879 27

We studied cellular interactions between human polymorphonuclear leukocytes (PMN) and lung cancer cell lines by investigating the influence of cancer cells on the production of leukotriene B4 (LTB4) and superoxide anion (O2-) by stimulated PMN. Of the nine cancer cell lines established from human lung cancers that we examined, H23 cells showed the highest LTA4 hydrolase activity. When PMN were stimulated by the calcium ionophore A23187 in the presence of H23 cells, the production of LTB4, 5(S)-hydroxyeicosatetraenoic acid (5-HETE), and 12(S)-hydroxyeicosatetraenoic acid (12-HETE) decreased in a dose-dependent manner. On the contrary, H23 did not inhibit O2- production by PMN. Two other cell lines (N417 and Q9) caused similar inhibition of LTB4 production by PMN. These three cancer cell lines alone did not generate any metabolites of the arachidonic acid (AA) lipoxygenase pathway or any O2- upon stimulation with A23187 alone. The addition of AA dose-dependently reversed the H23-induced inhibition of LTB4, 5-HETE, and 12-HETE production by PMN, suggesting inhibition at the phospholipase A2 (PLA2) level. Furthermore, addition of the cancer cell line Q9 inhibited 14C release from [14C]AA prelabeled PMN in a cell number-dependent manner in the buffer, with and without albumin. The supernatant of H23 cells also inhibited the production of LTB4 by PMN stimulated by A23187, as did the addition of H23 lysate or its 10(4) x g centrifugation supernatant. While neither the 10(5) x g supernatant (cytosol) nor the pellet (microsome) exhibited inhibitory activity, the combination of the separated cytosol and microsomal fractions restored the inhibitory activity. Furthermore, addition of the 10(4) x g supernatant of Q9 lysate to partially purified human cytosolic PLA2 inhibited PLA2 activity in a dose-dependent manner. Our results indicate that the lung cancer cell lines used in our study inhibit LTB4 production by human PMN through inhibition of phospholipase A2 activity, which may contribute to a predisposition to pulmonary infections in patients with lung cancer.
Am J Respir Cell Mol Biol 1996 Nov
PMID:Lung cancer cell lines inhibit leukotriene B4 production by human polymorphonuclear leukocytes at the level of phospholipase A2. 891 63

A full-length cDNA encoding the broad bean lipoxygenase VfLOX1 was isolated from a nodule cDNA library. The VfLOX1 gene was strongly expressed in nodules, and only weakly in roots. VfLOX1 transcripts were localized in the nodule parenchyma and in the cells surrounding the root stele.
Mol Plant Microbe Interact 1996 Dec
PMID:The Vicia faba lipoxygenase gene VfLOX1 is expressed in the root nodule parenchyma. 896 35

Mammalian lipoxygenases are implicated in the biosynthesis of inflammatory mediators, in the pathogenesis of atherosclerosis and in the process of blood cell differentiation and maturation. With respect to their reaction specificity, three major types of mammalian lipoxygenases (15-lipoxygenases, 12-lipoxygenases and 5-lipoxygenases) may be classified. Although this nomenclature is commonly used, the mechanistic reasons for the positional specificity of lipoxygenases are not well understood. We investigated the structural reasons for lipoxygenase specificity by a combination of chimera formation and site-directed mutagenesis, and identified phenylalanine 353 as primary determinant for the positional specificity of rabbit reticulocyte 15-lipoxygenase. Modeling of the enzyme-substrate interaction suggested that the alignment of arachidonic acid at the active site appears to be influenced by this residue. According to the substrate orientation, the 15-lipoxygenase may be differentiated from two types of mammalian 12-lipoxygenases.
J Mol Biol 1996 Dec 20
PMID:Phenylalanine 353 is a primary determinant for the positional specificity of mammalian 15-lipoxygenases. 900 Jun 36

Escherichia coli hemolysin (HlyA) has been identified as a potent inductor of phosphoinositide hydrolysis and related metabolic responses in neutrophils (Grimminger and colleagues, 1991, J. Clin. Invest. 88:1531-1539). In isolated perfused rabbit lungs, which harbor a large number of entrapped microvascular leukocytes, we investigated the effect of a low dose of HlyA on lipoxygenase product formation in the presence of exogenous free arachidonic acid (AA), eicosapentaenoic acid (EPA), or both precursor fatty acids. Leukotrienes (LT) and hydroxyeicosatetra(penta)enoic acids (HET[P]E) in the recirculating perfusate were quantified using high-performance liquid chromatography techniques. In the absence of exogenous precursor fatty acid supply, 0.02 hemolytic units/ml HlyA elicited only minor amounts of LTs and 5-HETE. AA, 10 microM, provoked the generation of limited quantities of LTB4, LTE4, and 5-HETE. Combined application of HlyA and AA caused a manifold amplification of 4-series LT and 5-HETE generation, with predominance of cysteinyl-LTs. EPA, 10 microM, elicited the synthesis of 5-series LTs accompanied by marked quantities of 5-HEPE. Dual stimulation with HlyA and EPA provoked exclusive generation of excessive quantities of all 5-series 5-lipoxygenase products. When HlyA was administered in the presence of both AA (10 microM) and EPA (10 microM), the n-3 fatty acid clearly turned out to be the preferred substrate, with ratios of the various 5-series to 4-series products ranging between 1.8 and 14.5. Moreover, the absolute quantities of AA-derived metabolites and the total sum of all 5-lipoxygenase products was markedly reduced under these conditions. We conclude that the HlyA-evoked 5-lipoxygenase product formation in the pulmonary vasculature of the rabbit is critically dependent on the presence of free precursor fatty acids. The profile of LTs suggests neutrophil (PMN)-related transcellular eicosanoid synthesis as a major underlying metabolic pathway. EPA represents the preferred substrate as compared with AA, resulting in a marked suppression of AA metabolite formation. Therapeutic attempts to provide n-3 fatty acids via the intravenous route may have a major impact on lipid mediator profiles in PMN-related inflammatory events.
Am J Respir Cell Mol Biol 1997 Mar
PMID:Synthesis of 4- and 5-series leukotrienes in the lung microvasculature challenged with Escherichia coli hemolysin: critical dependence on exogenous free fatty acid supply. 907 Jun 17

Two lipoxygenase (LOX) genes (tomloxA and tomloxB) are expressed in ripening tomato fruit, and tomloxA is also expressed in germinating seedlings. The 5'-upstream regions of these genes were isolated to study the regulatory elements involved in coordinating tomlox gene expression. Sequence analysis of the promoters did not reveal any previously characterized regulatory elements except for TATA and CAAT boxes. However, the sequence motif GATAcAnnAAtnTGATG was found in both promoters. Chimeric gene fusions of each tomlox promoter with the beta-glucuronidase reporter gene (gus) were introduced into tobacco and tomato plants via Agrobacterium-mediated transformation. GUS activity in tomloxA-gus plants during seed germination peaked at day 5 and was enhanced by methyl jasmonate (MeJa) treatment. No GUS activity was detected in tomloxB-gus seedlings. Neither wounding nor abscisic acid (ABA) treatment of transgenic seedlings modified the activity of either promoter. During fruit development, GUS expression in tomloxA-gus tobacco fruit increased 5 days after anthesis (DAA) and peaked at 20 DAA. In tomloxB-gus tobacco fruit, GUS activity increased at 10 DAA and peaked at 20 DAA. In transgenic tomato fruit, tomloxA-gus expression was localized to the outer pericarp during fruit ripening, while tomloxB-gus expression was localized in the outer pericarp and columella. These data demonstrate that the promoter regions used in these experiments contain cis-acting regulatory elements required for proper regulation of tomlox expression during development and for MeJa-responsiveness.
Plant Mol Biol 1997 Mar
PMID:Developmental regulation of two tomato lipoxygenase promoters in transgenic tobacco and tomato. 910 7

We investigated the expression and accumulation pattern of lipoxygenase isoforms throughout the maize plant life. Two forms of lipoxygenase L1 and L2 have been identified as acidic proteins of 100 kDa (pI 6.4) and 90 kDa (pI 5.5-5.7) which accumulate in dry embryos and in various organs of maize seedlings. In young embryos, only the L2 form was detected and accumulation of L2 mRNA decreased during embryo development. Identification of lipoxygenases from in vivo and in vitro synthesized proteins indicates that similar levels of both L1 and L2 forms accumulated during treatment with abscisic acid, (ABA) gibberellic acid (GA3) and jasmonic acid (JA). However, differences in the activity of both enzymes were detected. By using an antiserum directed against purified L2 we isolated and characterized a partial cDNA clone of maize embryos encoding a lipoxygenase. The deduced amino acid sequence of L2 cDNA shares 78% identity with the rice L2 protein, and 51-56% identity with lipoxygenases from the dicotyledonous plants soybean and Arabidopsis. DNA blot analysis indicated that maize contains a family of lipoxygenase genes which are presently being characterized.
Plant Mol Biol 1997 Mar
PMID:Molecular characterization of L2 lipoxygenase from maize embryos. 913 52

Six substituted aryloxy diamines, synthesized as potential new antiinflammatory agents, were tested in vivo and in vitro in order to evaluate their biological activities. These derivatives reduced significant carrageenin rat paw edema and showed antiproteolytic activity. The in vitro inhibition of soybean lipoxygenase ranged from 41-77%. The results are discussed from the view of structural modifications.
Res Commun Mol Pathol Pharmacol 1997 Mar
PMID:1-[3-(Aryloxy) propyl]-diamines: a new class of non-steroidal basic antiinflammatory agents. Structure-activity studies: Part II. 914 38


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