Involvement Of Lipoxygenase Research Articles

Single and multiple inhibitors of the biosynthesis of 5-, 12-, 15-lipoxygenase products derived from cinnamyl-3,4-dihydroxy-α-cyanocinnamate: Synthesis and structure-activity relationship.

The involvement of lipoxygenases in various pathologies, combined with the unavailability of safe and effective inhibitors of the biosynthesis of their products, is a source of inspiration for the development of new inhibitors. Based on a structural analysis of known inhibitors of lipoxygenase products biosynthesis, a comprehensive structure-activity study was carried out, which led to the discovery of several novel compounds (16a-c, 17a) demonstrating promising potency to inhibit the biosynthesis of products of 5-, 12- and 15-LO. Compounds 16b and 16c outperformed zileuton (1), the only FDA-approved 5-LO inhibitor, as well as known inhibitors such as caffeic acid phenethyl ester (CAPE (2)) and cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC (4)). However, the introduction of a cyano group at the α-position of the carbonyl abolished the activity. Compounds 16a and 17a also inhibited the biosynthesis of 12- and 15-LO products. Compounds 16a, 17a far surpassed baicalein, a known 12-LO inhibitor, as inhibitors of 12-LO products biosynthesis. Compound 17a and CDC (4) showed equivalent inhibition of LO products, proposing that the double bond in the ester moiety is not necessary for the inhibitory activity. The introduction of the cyano group, as in compound 17a, at the α-position of the carbonyl in compound 16a significantly reduced the inhibitory activity against the biosynthesis of 15-LO products. In addition to the interactions with residues His372 and Phe421 also found with zileuton and CAPE, compounds 16a and 16c each interact with residue His367 as shown by molecular docking. This new interaction may explain their high affinity with the 5-LO active site.

Bacterial and Protozoan Lipoxygenases Could be Involved in Cell-to-Cell Signaling and Immune Response Suppression.

Lipoxygenases are found in animals, plants, and fungi, where they are involved in a wide range of cell-to-cell signaling processes. The presence of lipoxygenases in a number of bacteria and protozoa has been also established, but their biological significance remains poorly understood. Several hypothetical functions of lipoxygenases in bacteria and protozoa have been suggested without experimental validation. The objective of our study was evaluating the functions of bacterial and protozoan lipoxygenases by evolutionary and taxonomic analysis using bioinformatics tools. Lipoxygenase sequences were identified and examined using BLAST, followed by analysis of constructed phylogenetic trees and networks. Our results support the theory on the involvement of lipoxygenases in the formation of multicellular structures by microorganisms and their possible evolutionary significance in the emergence of multicellularity. Furthermore, we observed association of lipoxygenases with the suppression of host immune response by parasitic and symbiotic bacteria including dangerous opportunistic pathogens.

Lipoxygenase-induced autoxidative degradation of terrestrial particulate organic matter in estuaries: A widespread process enhanced at high and low latitude

There exists a substantial amount of research on abiotic (e.g. photochemical) degradation pertaining to organic matter (OM) in the marine realm. While recent research has shown its importance in the degradation of terrestrial particulate OM (TPOM), the mechanisms involved in the induction of autoxidation in estuaries remain unclear. In this study, we propose for the first time the involvement of lipoxygenase (LOX) activity in the induction of autoxidation in mixed waters. The observation of unusual profiles of palmitoleic acid oxidation products and the presence of jasmonic acid in suspended particulate matter (SPM) collected close to the Rhône River, as well as in samples from the Mackenzie and Amazon rivers, is attributed to strong LOX activity. We show the role played by salinity in the induction of this LOX activity and provide an explanation for the differences in estuarine autoxidation level. At high latitude, lower temperatures and irradiance favor photooxidative damage to higher plant debris and, consequently, hydroperoxide production. High hydroperoxide content strongly contributes to LOX activation in mixed waters. The high resulting LOX activity enhances alkoxyl radical production and thus autoxidation. On the contrary, at low latitude, photooxidative effects are limited, and riverine autoxidation is favored. The higher hydroperoxide content of TPOM may, as a consequence, thereby also contribute to a high level of LOX activity and autoxidation in estuaries. In temperate zones, land and riverine photooxidative and autoxidative damage is limited, unlike estuaries where we observed significant LOX-induced and autoxidative damage.

Lipoxygenases modulate the effect of glutoxim on Na+ transport in the frog skin epithelium

Using voltage-clamp technique, the involvement of lipoxygenases in the effect of immunomodulatory drug glutoxim on Na+ transport in frog skin was investigated. It was shown for the first time that preincubation of the skin with lipoxygenase inhibitors caffeic acid, baicalein, and nordihydroguaiaretic acid significantly decreases the stimulatory effect of glutoxim on Na+ transport. The data suggest the involvement of lipoxygenase oxidation pathway of arachidonic acid metabolism in the glutoxim effect on Na+ transport in frog skin epithelium.

Governing Mechanism of Phospholipids Peroxidation via 15-Lipoxygenase, A Key Player in Ferroptosis Cell Death Pathway

Ferroptosis is a newly discovered cell death pathway that is characterized by the production of lipid hydroperoxides. Although the exact lipid peroxidation pathways have not been identified, recent findings indicate the involvement of lipoxygenases (LOXs), particularly, 15LOX acting directly —independently from phospholipases— on the membrane. Here, a combination of computational approaches was used to study interactions of human 15LOX-2 with a membrane, and to identify preferred phospholipid substrates for this enzyme. Using molecular docking modeling, the binding poses and the binding affinities of various esterified lipids and arachidonic acid —a known substrate of LOXs—were compared. It has been shown that ferroptosis-triggering events occur predominantly in the endoplasmic reticulum. Therefore, coarse-grained molecular dynamics (CGMD) simulations were applied to study the interactions of 15LOX-2 with an endoplasmic reticulum membrane mimic. Our modeling data revealed that phosphatidylethanolamine and phosphatidylinositol are the most likely membrane substrates for 15LOX-2. CGMD simulations (2 μs runs) confirmed that the amino-terminal β-barrel domain (called PLAT) of 15LOX-2 is responsible for membrane binding. This domain entered deeply into the membrane. To establish the positioning of the catalytic site's opening and its orientation with respect to the membrane surface, we reconstructed an atomistic model based on the CGMD data. The opening of the J-shaped catalytic site invariably oriented itself toward the membrane surface facilitating phospholipid hydroperoxidation. Accordingly, we propose a model indicating that the PLAT domain strongly entangles 15-LOX in the membrane providing accessibility of the active site to esterified lipids embedded in the membrane. These data have been supported by grants P01HL114453, U19AI068021 and HFSP-RGP0013/2014.

Nordihydroguaiaretic acid activates hTRPA1 and modulates behavioral responses to noxious cold in mice.

Nordihydroguaiaretic acid (NDGA) is a major biologically active component of the creosote bush, Larrea tridentate, widely used in unregulated therapies. NDGA is a lipoxygenase inhibitor while a derivative, terameprocol, has been trialed as a chemotherapeutic agent. When investigating fatty acid activation of the human transient receptor potential cation channel subfamily A, member 1 (hTRPA1), we found that NDGA activated the channel. Here we investigate the actions of NDGA and terameprocol at hTRPA1 and the consequences of this for noxious cold sensitivity in mice. hTRPA1 was stably expressed in HEK 293 cells (HEK 293-TRPA1) and channel activity examined by measuring changes in intracellular calcium ([Ca]i) using a fluorescent dye and activation of membrane currents using patch clamp electrophysiology. The effects of local NDGA and terameprocol application on acetone-induced paw flinching were examined in mice. NDGA (pEC50 of 5.4 ± 0.1, maximum change in fluorescence of 385 ± 30%) and terameprocol (pEC50 4.5 ± 0.2, maximum 550 ± 75%) increased [Ca]i in HEK 293-hTRPA1 cells. NDGA also induced an increase in membrane conductance in HEK 293-hTRPA1 cells. These effects were prevented by the TRPA1 antagonist HC-030031, and were dependent on the presence of Cys621, Cys 641, and Cys 665 in hTRPA1. Neither NDGA nor terameprocol alone produced spontaneous pain behaviors in mice after hind paw injection, but both enhanced responses to acetone. NDGA and terameprocol are efficacious activators of TRPA1. NDGA should be used with care to probe lipoxygenase involvement in nociception while TRPA1 activity should be considered when considering use of these drugs in humans.

Modelling the stability of lycopene-rich by-products of tomato processing

Tomato by-products were produced by puree manufacturing from heat-stabilised fruits and raw fruits to simulate both conventional and innovative processing technologies. By-products were freeze-dried, ground and stored in five relative humidity environments in the range 11–75%, for 4 months at 30 °C. The aims were: (a) to investigate the effect of heating applied during tomato processing on by-product hygroscopicity and stability, (b) to find out the optimal water activity ( a w) range for by-product stability. Hygroscopicity was studied by applying the Guggenheim–Anderson–de Boer (GAB) model. By-product stability was studied by evaluating the kinetics of lycopene, β-carotene, rutin and chlorogenic acid degradation and the changes in Hunter’s colourimetric parameters during storage. By-products obtained from heat-stabilised fruit and raw fruits had the same hygroscopicity, with an average estimated n sm value of 0.080 ± 0.013 kg water/kg dry solids, corresponding to the mean a w of 0.44 and the confidence interval of 0.31 < a w < 0.51 (on the 95% probability level). During storage, in both by-products the rate constant for lycopene degradation was maximum at the a w level of 0.17 (half-life time was 38 d); it then decreased by more than threefold with increasing the a w level up to 0.75 (half-life time was 138 d). β-Carotene degradation rates had the same order of magnitude as those of lycopene and decreased with increasing the a w level in the heat-treated by-product. However, β-carotene degradation was accelerated at a w levels ⩾0.56 in the by-product obtained from raw fruits, suggesting the involvement of lipoxygenase. Chlorogenic acid and rutin were more stable than the carotenoids and showed an opposite dependence of their stability on the a w level, being significantly degraded only at the highest a w level. The degradation of these phenolics was higher in the by-product obtained from raw fruits, indicating the likely involvement of polyphenol oxidase. The colour difference Δ E represented the sum of different degradation processes, indicating that for maximum stability, i.e. minimal Δ E variation, a dehydration level corresponding to 0.22 ⩽ a w ⩽ 0.56, has to be achieved and then maintained by preventing moisture exchanges with both environment and other food components.

Involvement of lipoxygenase in elicitor-stimulated sanguinarine accumulation in Papaver somniferum suspension cultures

The involvement of lipoxygenase (LOX, EC 1.13.11.12) in elicitor-induced opium poppy defense response was investigated. Papaver somniferum L. suspension cultures were treated with abiotic elicitor methyl jasmonate (MJ), fungal elicitor (Botrytis cinerea homogenate) and phenidone (specific inhibitor of LOX) to determine the involvement of this enzyme in production of sanguinarine, the major secondary metabolite of opium poppy cultures. P. somniferum suspension cultures responded to elicitor treatment with strong and transient increase of LOX activity followed by sanguinarine accumulation. LOX activity increased in elicited cultures, reaching 9.8 times of the initial value at 10 h after MJ application and 2.9 times after B. cinerea application. Sanguinarine accumulated to maximal levels of 169.5 ± 12.5 μg g⁻¹ dry cell weight in MJ-elicited cultures and 288.0 ± 10.0 μg g⁻¹ dry cell weight in B. cinerea-elicited cultures. The treatment of cells with phenidone before elicitor addition, significantly reduced sanguinarine production. The relative molecular weight of P. somniferum LOX (83 kDa) was estimated by using immunobloting and its pH optimum was shown to be pH 6.5.

Lipoxygenase and cyclooxygenase inhibitors reveal a complementary role of arachidonic acid derivatives in pregnant human myometrium

The aim of this study was to assess the involvement of lipoxygenase (LOX) metabolic pathways in uterine tissues from pregnant women as well as the combined inhibition of LOX and cyclooxygenase (COX) on contractile activity. Uterine biopsies were performed from consenting women undergoing elective caesarean sections at term (n = 24). Western blot analysis and isometric tension measurements were performed in vitro on fresh human myometrial strips. Concentration-response curves to arachidonic acid (AA) 861 and baicalein (5- and 12-LOX inhibitors, respectively) were performed. The combined effects of baicalein and indomethacin were also assessed. Contractile activities were quantified by calculating both amplitude and the area under the curve over 20 minute periods. 5- and 12-LOX were present in all tested tissues. Addition of AA861 or baicalein resulted in tocolytic effects (P < .05). Finally, the combined inhibition of both COX and 12-LOX pathways resulted in additive tocolytic effects. 5- and 12-LOX pathways modulate human myometrium contractility.

UVB Radiation Induces Apoptosis in Keratinocytes by Activating a Pathway Linked to “BLT2-Reactive Oxygen Species”

The role of reactive oxygen species (ROS) in UVB-induced apoptosis has been established, but the molecular mechanisms of their production in response to UVB irradiation in keratinocytes are not well understood. In this study, we demonstrate that levels of BLT2, a low-affinity leukotriene B(4) receptor, and its ligands (LTB(4) and 12(S)-HETE) are greatly increased by UVB irradiation and are responsible for the UVB-induced ROS generation in human keratinocytes. Blockade of BLT2 with a BLT2-specific antagonist, LY255283, or with siBLT2 attenuated ROS production and apoptotic cell death detected by a number of criteria. Moreover, we found that the NADPH oxidase family protein Nox1 lies downstream of BLT2 and mediates UVB-induced ROS production and apoptosis. Topical treatment of mouse epidermal skin with LY255283 gave significant protection against UVB-induced sunburn-associated apoptotic damage. Finally, when BLT2-overexpressing transgenic mice were irradiated with UVB, we observed more extensive skin apoptosis. Taken together, our results demonstrate that a "BLT2-Nox1"-linked pathway has a crucial role in UVB-induced ROS generation and mediates apoptosis in human keratinocytes.

W1726 Lansoprazole, a Proton Pump Inhibitor, Mediated Anti-Inflammatory Effect in Gastric Mucosal Cells Through the Induction of Heme Oxygenase-1 Via the Activation of NRF2 and the Oxidation of Keap1

Dietary fats, which increase the risk of prostate cancer, stimulate release of intestinal neurotensin (NT), a growth-promoting peptide that enhances the formation of arachidonic acid metabolites in animal blood. This led us to use PC3 cells to examine the involvement of lipoxygenase (LOX) and cyclooxygenase (COX) in the growth effects of NT, including activation of EGF receptor (EGFR) and downstream kinases (ERK, AKT), and stimulation of DNA synthesis. NT and EGF enhanced [3H]-AA release, which was diminished by inhibitors of PLA2 (quinacrine), EGFR (AG1478) and MEK (U0126). NT and EGF phosphorylated EGFR, ERK and AKT, and stimulated DNA synthesis. These effects were diminished by PLA2 inhibitor (quinacrine), general LOX inhibitors (NDGA, ETYA), 5-LOX inhibitors (Rev 5901, AA861), 12-LOX inhibitor (baicalein) and FLAP inhibitor (MK886), while COX inhibitor (indomethacin) was without effect. Cells treated with NT and EGF showed an increase in 5-HETE levels by HPLC. PKC inhibitor (bisindolylmaleimide) blocked the stimulatory effects of NT, EGF and 5-HETE on DNA synthesis. We propose that 5-LOX activity is required for NT to stimulate growth via EGFR and its downstream kinases. The mechanism may involve an effect of 5-HETE on PKC, which is known to facilitate MEK-ERK activation. NT may enhance 5-HETE formation by Ca2+-mediated and ERK-mediated activation of DAG lipase and cPLA2. NT also upregulates cPLA2 and 5-LOX protein expression. Thus, the growth effects of NT and EGF involve a feed-forward system that requires cooperative interactions of the 5-LOX, ERK and AKT pathways.

Lipoxygenase Involvement in Ripening Strawberry

The enzymatic activity, subcellular localization, and immunolocalization of plant lipoxygenase (LOX) in strawberry fruits (Fragaria x ananassa, Duch) were investigated. Chemical and enzymatic properties of LOX have been characterized, and the LOX capability of oxygenating free and esterified unsaturated fatty acids into C6 volatile aldehydes has been confirmed. Fruits at unripe, turning, and ripe stages were analyzed for LOX activity and protein localization by Western blots, two-dimensional electrophoresis, and immunolocalization analyses. The ability of strawberry tissues to in vivo metabolize linolenic acid or linoleic acid into C6 volatile aldehydes and the LOX products was also analyzed. Analysis of strawberry proteins showed that a number of LOX forms, corresponding to at least two mobility groups of approximately 100 and 98 kDa and pI values ranging between 4.4 and 6.5, were present. Confocal and electron microscopy analyses support the idea that LOX proteins are associated to lipid-protein aggregates. Both exogenously supplied linoleate and linolenate were converted into hexanal and trans-2-hexenal at the three fruit-ripening stages. Our experiments suggest the presence of different LOX isoforms in strawberry fruits and that the lipoxygenase-hydroperoxide lyase pathway plays a role in converting lipids to C6 volatiles during ripening.

Effects of lipoxygenase and of chemical oxidising agent potassium iodate on rheological properties of durum dough

SummaryTo study the involvement of lipoxygenase (LOX) and oxidising agent potassium iodate (KIO3) in rheological behaviour of dough, mixograph and alveograph tests were performed using durum cultivars differing for quality and endogenous levels of LOX. Both tests were done in standard condition and with the adding of KIO3 and of LOX and/or its substrate, utilised singly or in different combinations. The effects of these treatments were related to change of ‐SH and S–S content in relative mixograph dough. The mixograph and alveograph responses showed that the KIO3 had an improving effect on dough tenacity and that the adding of LOX system enhanced this trend; on the contrary, the LOX system alone seemed not affect mixing stability. No relation was found between rheological responses and ‐SH and S–S content in the mixograph doughs. The results obtained could suggest that in durum wheat the main effect of LOX could be ascribable to bleaching action because of the co‐oxidation of carotenoid pigments.

Involvement of arachidonic acid metabolism and EGF receptor in neurotensin-induced prostate cancer PC3 cell growth

Dietary fats, which increase the risk of prostate cancer, stimulate release of intestinal neurotensin (NT), a growth-promoting peptide that enhances the formation of arachidonic acid metabolites in animal blood. This led us to use PC3 cells to examine the involvement of lipoxygenase (LOX) and cyclooxygenase (COX) in the growth effects of NT, including activation of EGF receptor (EGFR) and downstream kinases (ERK, AKT), and stimulation of DNA synthesis. NT and EGF enhanced [ 3H]-AA release, which was diminished by inhibitors of PLA2 (quinacrine), EGFR (AG1478) and MEK (U0126). NT and EGF phosphorylated EGFR, ERK and AKT, and stimulated DNA synthesis. These effects were diminished by PLA2 inhibitor (quinacrine), general LOX inhibitors (NDGA, ETYA), 5-LOX inhibitors (Rev 5901, AA861), 12-LOX inhibitor (baicalein) and FLAP inhibitor (MK886), while COX inhibitor (indomethacin) was without effect. Cells treated with NT and EGF showed an increase in 5-HETE levels by HPLC. PKC inhibitor (bisindolylmaleimide) blocked the stimulatory effects of NT, EGF and 5-HETE on DNA synthesis. We propose that 5-LOX activity is required for NT to stimulate growth via EGFR and its downstream kinases. The mechanism may involve an effect of 5-HETE on PKC, which is known to facilitate MEK-ERK activation. NT may enhance 5-HETE formation by Ca 2+-mediated and ERK-mediated activation of DAG lipase and cPLA2. NT also upregulates cPLA2 and 5-LOX protein expression. Thus, the growth effects of NT and EGF involve a feed-forward system that requires cooperative interactions of the 5-LOX, ERK and AKT pathways.

Short-chain fatty acids alter tight junction permeability in intestinal monolayer cells via lipoxygenase activation

Objective Involvement of lipoxygenase (LOX) and cyclo-oxygenase (COX) on cellular differentiation or apoptosis induced by butyrate has been reported recently, but the effect on tight junction (TJ) permeability has not been reported. One major activity of butyrate and, to a lesser extent, propionate is to modulate gene transcription via histone acetylation by their histone deacetylase inhibitor activity. In this study, we evaluated the activation of LOX and COX in TJ permeability changes by short-chain fatty acids, butyrate, propionate, and acetate in intestinal monolayer cells and their possible mechanism by histone acetylation. Methods The effects of LOX and COX inhibitors on TJ permeability and the expression of LOX or COX mRNA induced by short-chain fatty acids were investigated in Caco-2 cells using Transwell chambers. The effects of hydroxyeicosatetraenoic acid (a product of LOX) on TJ permeability were also evaluated. The effects of short-chain fatty acids were compared with those of trichostatin A (histone deacetylase inhibitor). Results A LOX inhibitor clearly inhibited the effect of butyrate on TJ permeability, whereas COX inhibitors did not. The LOX and COX inhibitors partly inhibited the effects of propionate but not of acetate. Butyrate increased LOX mRNA expression, and hydroxyeicosatetraenoic acid and trichostatin A mimicked its effect. Conclusion These results suggest that short-chain fatty acids, especially butyrate, induce TJ permeability changes through LOX activation through histone acetylation.

Involvement of phospholipase A2 and lipoxygenase in lipopolysaccharide-induced inducible nitric oxide synthase expression in glial cells

The present study underlines the importance of phospholipase A2 (PLA2)- and lipoxygenase (LO)-mediated signaling processes in the regulation of inducible nitric oxide synthase (iNOS) gene expression. In glial cells, lipopolysaccharide (LPS) induced the activities of PLA2 (calcium-independent PLA2; iPLA2 and cytosolic PLA2; cPLA2) as well as gene expression of iNOS. The inhibition of cPLA2 by methyl arachidonyl fluorophosphates (MAFP) or antisense oligomer against cPLA2 and inhibition of iPLA2 by bromoenol lactone reduced the LPS-induced iNOS gene expression and NFkappaB activation. In addition, the inhibition of LO by nordihydroguaiaretic acid (NDGA; general LO inhibitor) or MK886 (5-LO inhibitor), but not baicalein (12-LO inhibitor), completely abrogated the LPS-induced iNOS expression. Because NDGA could abrogate the LPS-induced activation of NFkappaB, while MK886 had no effect on it, LO-mediated inhibition of iNOS gene induction by LPS may involve an NFkappaB-dependent or -independent (by 5-LO) pathway. In contrast to LO, however, the cyclooxygenase (COX) may not be involved in the regulation of LPS-mediated induction of iNOS gene because COX inhibition by indomethacin (general COX inhibitor), SC560 (COX-1 inhibitor), and NS398 (COX-2 inhibitor) affected neither the LPS-induced iNOS expression nor activation of NFkappaB. These results indicate a role for cPLA2 and iPLA2 in LPS-mediated iNOS gene induction in glial cells and the involvement of LO in these reactions.

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by beta-amyloid peptide.

The cyclo-oxygenase (COX) and lipoxygenase (LOX) pathways belong to the eicosanoid synthesis pathway, a major component of the chronic inflammatory process occurring in Alzheimer's disease (AD). Clinical studies reported beneficial effects of COX inhibitors, but little is known about the involvement of LOXs in AD pathogenesis. beta-amyloid peptide (A beta) accumulation contributes to neurodegeneration in AD, but mechanisms underlying A beta toxicity have not been fully elucidated yet. Here, using an antisense oligonucleotide-based strategy, we show that blockade of 12-LOX expression prevents both A beta-induced apoptosis and overexpression of c-Jun, a factor required for the apoptotic process, in cortical neurons. Conversely, the 12-LOX metabolite, 12(S)-HETE (12(S)-hydroxy-(5Z, 8Z, 10E, 14Z)-eicosatetraenoic acid), promoted c-Jun-dependent apoptosis. Specificity of the 12-LOX involvement was further supported by the observed lack of contribution of 5-LOX in this process. These data indicate that blockade of 12-LOX expression disrupts a c-Jun-dependent apoptosis pathway, and suggest that 12-LOX may represent a new target for the treatment of AD.

Evidence for the involvement of lipoxygenase in the oxidative processes associated with the appearance of green staining alteration in the Gordal olive

AbstractLipoxygenase (LOX) activity and chloroplast pigment content were monitored during fruit growth in Gordal and Manzanilla olive varieties (Olea europaea regalis and Olea europaea pomiformis respectively). At all growth stages, LOX activity was greater in Gordal than in Manzanilla, and in both varieties, enzymatic activity peaks coincided with the maximum presence of oxidised chlorophyll pigments in the fruits. The higher lipid peroxidation potential measured directly in vitro and indirectly in vivo in the Gordal variety and its correspondence with higher contents of oxidised catabolites of chlorophyll suggested a greater tendency and sensitivity of this variety to oxidative processes. This could also explain the high organelle disorganisation levels reached during industrial processing of the fruit, allowing the formation of copper–chlorophyll complexes associated with the green staining alteration that affects Gordal olives. Copyright © 2003 Society of Chemical Industry

45 Cyclooxygenase and lipoxygenase involvement in increased uterine contractility due to endogenous mast cell degranulation

45 Cyclooxygenase and lipoxygenase involvement in increased uterine contractility due to endogenous mast cell degranulation

Time-course of lipoxygenase, antioxidant enzyme activities and H2 O2 accumulation during the early stages of Rhizobium-legume symbiosis.

• The involvement of lipoxygenase and antioxidant enzyme activities as well as hydrogen peroxide (H2 O2 ) accumulation are reported during early infection steps in alfalfa (Medicago sativa) roots inoculated either with a wild type Sinorhizobium meliloti or with a mutant defective in Nod-factor synthesis (Nod C- ). • Compatibility between M. sativa and Rhizobium correlates, at least in part, with an increase in the activities of these enzymes, particularly catalase and lipoxygenase, during the preinfection period (up to 12h). The mutant strain, defective in Nod-factor biosynthesis, showed a decrease in all enzyme activities assayed, and an increase in H2 O2 accumulation. • Enhancement of scavenging activities for several reactive oxygen species correlated with compatibility of the S. meliloti-alfalfa symbiosis, whereas the Nod C- strain triggered a defence response. Nod factors were essential to suppress this response. • Increase in lipoxygenase and lipid hydroperoxide decomposing activities, observed during the first hours after inoculation with a compatible strain, could be related to tissue differentiation and/or the production of signal molecules involved in autoregulation of nodulation by the plant.