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At least 973 records · Page 54Linked to original sources
PubMed2006

Structural elucidation and biological activity of acyl-homoserine lactones from the phytopathogen Pantoea ananatis Serrano 1928.

In Gram-negative bacteria, the acyl-homoserine lactones (acyl-HSLs) are the main signaling substances employed in cell-to-cell communication systems. This paper describes the chemical characterization of acyl-HSLs produced by the worldwide-spread phytopathogen Pantoea ananatis (Serrano 1928) by using gas chromatography-electron impact mass spectrometry. The absolute configuration of the major identified substance, (S)-(--)-N-hexanoyl-HSL, was determined with gas chromatography-flame ionization detection with a chiral capillary column. Biological activities of extracts, fractions, and synthetic products were evaluated with the specific reporter Agrobacterium tumefaciensNTL4(pZLR4) in beta-galactosidase expression assays.

4-Butyrolactone↗
PubMed1990

A comparison of the affinities of rat (Na+ + K+)-ATPase isozymes for cardioactive steroids, role of lactone ring, sugar moiety and KCl concentration.

Binding experiments at equilibrium were performed to study pharmacological properties of isozymes of (Na+ + K+)-ATPase from rat tissues. Experiments were performed on brain (alpha 3 isozyme), kidney (alpha 1 isozyme) and heart microsomes (alpha 1 and alpha 2 isozymes). Affinity of series of ouabain and digoxin derivatives was studied in competition experiments. It was observed that: (i) ouabain and digoxin had higher affinity (P less than 0.01) for alpha 3 isozyme (Kd of 0.071 +/- 0.004 and 0.066 +/- 0.001 microM, respectively) than for alpha 1 isozyme (Kd of 15.9 +/- 0.8 and 1.78 +/- 0.46 microM, respectively) and alpha 2 isozyme (Kd of 0.26 +/- 0.04 and 0.15 +/- 0.06 microM, respectively); (ii) saturation of the C20-C22 bond on the C17 beta lactone ring present in ouabain and digoxin markedly decreased the drug affinity for all isozymes (P less than 0.01); and (iii) suppression of the C3 beta osidic chain decreased the affinity of ouabain and digoxin to a higher extent for alpha 2 and alpha 3 than for alpha 1 (P less than 0.01). The presence of 10 mM KCl in the incubation medium decreased ouabain affinity for the alpha 1 isozyme to a much higher extent (Kd increase of about 20-fold) than for the other isozymes (Kd increase of about 2-fold). The results show that the isozymes of (Na+ + K+)-ATPase from rat tissue are differently sensitive to changes in the substituents of the cardioactive steroids and to the presence of 10 mM KCl.

Animals↗
PubMed1992

Observations of synaptic efficacy and paired-pulse facilitation in area CA1 of hippocampal slices from coriaria lactone-kindled rats.

The changes of population spike(PS)/population excitatory postsynaptic potential (EPSP) slope relationship and paired-pulse facilitation (PPF) were primarily investigated with extracellular recording in stratum pyramidale to stimulation of Schaffer collaterals in CA1 region of hippocampal slices from coriaria lactone (CL)-kindled and control rats. The results were as follows: (1) neither spontaneous nor evoked epileptiform bursts were found in all hippocampal slices from CL-kindled and control rats; (2) the synaptic efficacy, expressed by the ratio of PS/EPSP slope, at low stimulation intensity ranging from 10-30% of its maximum was significantly increased on CL-kindled rats (P less than 0.05); and (3) although PPF was found in all slices, the PPF strength only at stimulation intensity of 10 and 20% of maximum was augmented remarkably in CL-kindled rats (P less than 0.002 and 0.024, respectively). According to the results from our previous work, we suggested that the increment of PS/EPSP slope ratio and PPF strength at low stimulation intensity may result from the potentiation of excitatory synaptic activity or/and the change of intrinsic excitability of pyramidal neurons.

Action Potentials↗
PubMed1990

Studies on the N-acetyl-beta-D-hexosaminidase B from germinating Lupinus luteus L. seeds. II. Mechanism and inhibition with some 2-acetamido-2-deoxyaldono(1----4)lactones.

The N-acetyl-beta-D-hexosaminidase B of germinating yellow lupin seeds catalyzed the hydrolysis of both p-nitrophenyl-N-acetyl-beta-D-glucosaminide and -galactosaminide substrates. The investigation of the pH dependence of the kinetic parameters (Vmax and Vmax/Km) demonstrated that two common ionizable groups (probably two carboxyl groups) play an essential role in the catalysis. That is, the enzyme has a lysozyme-like splitting mechanism, and the possibility of an anchimeric assistance provided by the acetamido group seems to be negligible. The presence of a deprotonated carboxyl group near the glycosidic linkage was also supported by inhibition with 1-thio substrate analogues. On the other hand, some 2-acetamido-2-deoxyaldono(1----4)lactones proved to be effective inhibitors of the hexosaminidase with the exception of the D-arabinose derivative, which can be explained by high stereospecificity in the binding.

Amino Sugars↗
PubMed1992

The effect of pH on the thermal resistance of Clostridium sporogenes (PA 3679) in asparagus purée acidified with citric acid and glucono-delta-lactone.

The influence of type of acid, pH and temperature on heat resistance of Clostridium sporogenes (PA 3679) spores were investigated in white asparagus pureé acidified with citric acid and glucono-delta-lactone (GDL). The pH values studied were: 4.5, 4.8, 5.1 and 5.4 at temperatures of 110, 115, 118 and 121 degrees C. The addition of citric acid and GDL to reduce pH significantly diminished heat resistance of the spores. The two acids investigated differed in their effect on heat resistance at the various pH-levels. The most pronounced effect was observed at the lower heat treatment temperatures investigated. The z values ranged from 10.24 to 13.09 degrees C in the asparagus purée with acids added and with significant differences between the two acids and the various pH levels.

Citrates↗
PubMed1995

Glucono-delta-lactone and citric acid as acidulants for lowering the heat resistance of Clostridium sporogenes PA 3679 in HTST working conditions.

The heat resistance of Clostridium sporogenes PA 3679 spores has been studied to establish the influence of acidification with glucono-delta-lactone (GDL) and citric acid on the thermal resistance parameters (DT and z) of this microorganism and to compare their effect with phosphate buffer and natural asparagus as reference substrates. A reduction in DT values was observed in asparagus purée as the acidification level increased with both acidulants although this effect was more evident at the lower treatment temperatures studied (121-127 degrees C). Citric acid was more effective for reducing the heat resistance of spores than GDL at all of the temperatures. The reduction in pH diminished the value of the z parameter, although it was necessary to lower the pH to 4.5 to obtain a significant reduction.

Citrates↗
PubMed1984

Structures of the dienoic lactones of horse sebum.

The C34, C36, and C38 dienoic omega-lactones were isolated from sebum of the horse (Equus caballus) and the double bond positions were determined by stepwise chemical dissection and analysis of the fragments. The structures found could be formed by delta 9-desaturation at the C18-stage of fatty acid biosynthesis followed by a second delta 9-desaturation when the chains reached C24, C26, C28, C30, or C32 and then addition of one to seven 2-carbon units. These findings provide insight into the dimensions and organization of the endoplasmic reticulum in cells of the sebaceous glands.

Animals↗
PubMed1993

High-performance liquid chromatographic analysis of the antitumour drug camptothecin and its lactone ring-opened form in rat plasma.

A sensitive high-performance liquid chromatographic (HPLC) method is described for the simultaneous determination of the antitumour drug camptothecin (I) and its lactone ring-opened form (II) in plasma. The sample pretreatment involved protein precipitation with cold methanol (-30 degrees C). The methanolic extract was injected directly onto the HPLC column. Chromatography was carried out with a LiChrosorb RP-18 column (particle size 5 microns) and a mobile phase composed of methanol-phosphate buffer (5 mM, pH 6.5)-0.3 M tetrabutylammonium phosphate solution (500:500:15, v/v/v). The column effluent was monitored spectrofluorimetrically with the excitation wavelength set at 369 nm and the emission wavelength at 426 nm. The chemical stabilities of camptothecin and the ring-opened form in aqueous solutions, in plasma and after methanolic extraction, were investigated. The proposed method was validated and utilized in pharmacokinetic studies with rats.

Animals↗
PubMed2004

Sesquiterpene lactones inhibit luciferase but not beta-galactosidase activity in vitro and ex vivo.

Reporter enzymes such as firefly luciferase or beta-galactosidase of Escherichia coli are frequently used to study transcriptional activity of genes and to investigate the effects of novel compounds on gene or transcription factor activity. It is generally assumed that the activity of these enzymes is unaffected by the treatment conditions. Therefore, this factor is not considered when interpreting the data obtained. Biologically active compounds such as sesquiterpene lactones (SLs) have also been tested in reporter gene assays for their influence on gene expression. Here we show in in vitro and ex vivo experiments that SLs inhibit firefly luciferase activity probably by direct targeting of the enzyme while beta-galactosidase remains almost completely unaffected. The loss of luciferase activity after SL treatment could be an effect of their sulfhydryl-modifying potency and the subsequent alteration of the enzyme's tertiary structure. These results demonstrate that the effect of the test substance on the reporter enzyme used should be taken into consideration when the transcriptional effect of novel compounds is investigated.

Animals↗
PubMed2004

Binding site for fungal beta-lactone hymeglusin on cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase.

We studied the molecular mechanism through which the fungal beta-lactone, hymeglusin, potently and specifically inhibits 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase. [(14)C]Hymeglusin covalently bound to purified rat liver and to recombinant hamster cytosolic HMG-CoA synthases. The enzyme activity was completely inhibited at a binding ratio of 1.6-2.0 mol [(14)C]hymeglusin/mol HMG-CoA synthase. Incubating the enzyme with 2 mM iodoacetamide (IAA) or 2 mM N-ethylmaleimide (NEM) but not with 1.0 mM diisopropyl fluorophosphates (DFP) completely inhibited the binding, suggesting that hymeglusin binds to a Cys residue of HMG-CoA synthase. Recombinant hamster HMG-CoA synthase labeled with [(3)H]hymeglusin was digested with V8 protease, and the [(3)H]peptide was purified by high performance liquid chromatography (HPLC). The sequence of the peptide was Ser-Gly-Asn-Thr-Asp-Ile-Glu-Gly-Ile-Asp-Thr-Thr-Asn-Ala-[(3)H]hymeglusyl Cys-Tyr-Gly-Gly-Thr-Ala-Ala-Val-Phe-Asn-Ala-Val-Asn-, which corresponds to the active site sequence (from Ser 115 to Asn 141) of hamster HMG-CoA synthase. These findings showed that hymeglusin inhibits hamster cytosolic HMG-CoA synthase by covalently modifying the active Cys 129 residue of the enzyme.

Amino Acid Sequence↗
PubMed2006

Prediction of the mechanism of action of omuralide (clasto-lactacystin beta-lactone) on human cathepsin A based on a structural model of the yeast proteasome beta5/PRE2-subunit/omuralide complex.

Cathepsin A (CathA) is a lysosomal serine carboxypeptidase that exhibits homology and structural similarity to the yeast and wheat serine carboxypeptidases (CPY and CPW) belonging to the alpha/beta-hydrolase fold family. Human CathA (hCathA) and CPW have been demonstrated to be inhibited by a proteasome (threonine protease) inhibitor, lactacystin, and its active derivative, omuralide (clasto-lactacystin beta-lactone), as well as chymostatin. A hCathA/omuralide complex model constructed on the basis of the X-ray crystal structures of the CPW/chymostatin complex and the yeast proteasome beta-subunit (beta5/PRE2)/omuralide one predicted that the conformation of omuralide in the active-site cleft of proteasome beta5/PRE2 should be very similar to that of chymostatin at the S1 catalytic subsites in the hCathA- and CPW-complexes. The relative positions of the glycine residues, i.e., Gly57 in hCathA, Gly53 in CPW, and Gly47 in beta5/PRE2, present in the oxyanion hole of each enzyme were also highly conserved. These results suggest that omuralide might inhibit hCathA and CPW at the S1 subsite in their active-site clefts through direct binding to the active serine residue.

Catalytic Domain↗
PubMed2004

Cynaropicrin, a sesquiterpene lactone, as a new strong regulator of CD29 and CD98 functions.

Cynaropicrin is a sesquiterpene lactone displaying immunomodulatory effects on the production of cytokine and nitric oxide from macrophages/monocytes. In this study we have examined inhibitory effect of cynaropicrin on activation of major adhesion molecules [CD29 (beta1 integrins), CD43, and CD98] on the cells assessed by U937 (promonocytic cells) homotypic aggregation. Cynaropicrin potently blocked CD29 (beta1 integrins)- and CD98-induced homotypic aggregation with IC(50) values of 3.46 and 2.98 microM, respectively, without displaying cytotoxicity. Similarly, flow cytometric analysis exhibited that cynaropicrin down-regulated strikingly surface level of CD29 and CD147, a functional regulator of CD98, but not CD43. More importantly, cynaropicrin inhibition was linked to blockade of extracellular signal-related kinase (ERK) activation and distinct from other enzyme inhibitors including rottlerin, propranolol, forskolin, and chloroquine, but not cytochalasin B. Therefore, our finding is the first demonstration that cynaropicrin may be a potent functional regulator of CD29 and CD98 via interrupting ERK activation which may be linked to cytoskeleton rearrangement, suggesting further application to CD29- and CD98-mediated diseases such as virus-induced chronic inflammation, and invasion, migration, and metastasis of leukocyte cancer cells.

Antigens, CD↗
PubMed2006

Reduced diversity of the human erythrocyte membrane sialic acids in polycythemia vera. Absence of N-glycolylneuraminic acid and characterisation of N-acetylneuraminic acid 1,7 lactone.

Sialic acids from the erythrocyte (RBC) membrane of a patient suffering from polycythemia vera, a malignant orphan disorder of hematopoietic cells, was studied using GC/MS. We found that the sialic acid diversity of these membranes was drastically reduced since only four entities were identified: Neu5Ac (91.5%) and its 1,7 lactone Neu5Ac1,7L (7.5%) which is absent in normal RBC, Neu4,5Ac(2) (0.50%) and Neu4,5Ac(2) 9Lt (0.50%); in normal RBC, Neu5,7Ac(2), Neu5,9Ac(2), Neu5Ac9Lt, Neu5Ac8S and Neu, as well as traces of Kdn, were also present. Neu5Gc and its O-alkylated or O-acetylated derivatives, which are considered by various authors as cancer markers, were not detected.

Erythrocyte Membrane↗
PubMed2005

Optimisation of a human neutrophil elastase assay and investigation of the effect of sesquiterpene lactones.

Neutrophil granulocytes are effector cells in innate and humoral immunity. They are involved in inflammatory processes by releasing pro-inflammatory enzymes, such as the human neutrophil elastase (HNE). We here report an optimisation of an HNE release assay using microplates. Special attention has been directed to overcome the often observed activation of neutrophils during isolation from fresh blood. This so-called basal stimulation can take place without addition of external stimulants and can cause severe problems during the assay. We demonstrated that bovine serum albumin (BSA), lipopolysaccharide (LPS), use of different blood donors, heparin and ethylenediaminetetraacetic acid (EDTA) do not cause basal stimulation, but may be due to mechanical stress and the immune system of the blood donor. Here, the number of eosinophils may play a role in the induction of activation. Basal stimulation was overcome when a hypertonic solution, such as sucrose- with N-(2-hydroxyethyl)-piperazine-N'-2-ethanesulfonic acid (HEPES) buffer, was used during centrifugation and the isolated granulocytes were left in phosphate buffered saline (PBS) for 30 min before stimulation. Sesquiterpene lactones (SLs), known for their anti-inflammatory activity were used for evaluation of the assay and were observed to inhibit HNE release at micromolar concentrations. Whereas N-formyl-methionyl-leucylphenylalanine (fMLP), platelet-activating factor (PAF) and basal stimulation resulted in similar IC50 values, phorbol-12-myristate-13-acetate (PMA) as a stimulant needed higher concentrations of SLs. The molecular inhibitory mechanism of SLs is discussed.

Enzyme Inhibitors↗
PubMed2005

DFT-GIAO study of aryltetralin lignan lactones: conformational analyses and chemical shifts calculations.

The conformational properties of polygamain and morelensin, two aryltetralin lignan lactones, have been investigated in both the gas-phase and chloroform solution using DFT calculations at the B3LYP/6-311G(d,p) level. Results indicate that the conformation of polygamain is very rigid. Thus, the conformational flexibility of its five-membered rings is considerably restricted as reflects the pseudorotational parameters of the corresponding envelope conformations. On the other hand, morelensin shows a notable conformational flexibility, which is mainly due to its two methoxy groups. Accordingly, 16 minimum energy conformations with relative energies smaller than 2.4 kcal/mol were detected. Furthermore, chemical shifts for 13C nuclei have been calculated using the GIAO method, results being compared with experimental data. A good agreement was found for both polygamain and morelensin.

Benzofurans↗
PubMed2005

Sesquiterpene lactones as inhibitors of IL-8 expression in HeLa cells.

Twenty-four structurally different SLs were studied for their inhibition on IL-8 production in HeLa229 cells and different IC50-values were obtained. QSAR analyses revealed that the alpha-methylene-gamma-lactone and the presence and reactivity of a second reaction center, expressed by LUMO2, are the most important descriptors for IL-8. Using two SLs as examples, we demonstrated that SLs prevent DNA binding of AP-1, which has binding sites in the IL-8 promoter together with NF-kappaB and C/EBP, and that this is probably due to directly targeting AP-1. p38 MAPK, which plays a role in AP-1 activation as well as in IL-8 regulation, was not influenced by SLs. These data show that NF-kappaB and AP-1, and consequently IL-8 may be interesting targets in antiinflammation research and that the small molecules of SLs may be powerful candidates with promising properties for therapeutic modulation of the inflammatory response.

Base Sequence↗