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)

Recently there has been a moderate resurgence in the use of flax-seed in a variety of ways including bread. The scientific basis of its use is very limited. There is some claim for beneficial effects in cancer and lupus nephritis. These claims could be due to its ability to scavenge oxygen radicals. However, its antioxidant activity is not known. Recently a method has been developed to isolate secoisolariciresinol diglucoside (SDG) from defatted flax-seed in large quantity (patent pending). We investigated the ability of SDG to scavenge .OH using high pressure liquid chromatography (HPLC) method. .OH was generated by photolysis of H2O2 (1.25-10.0 mumoles/ml) with ultraviolet light and was trapped with salicylic acid which is hydroxylated to produce .OH-adduct products 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA. H2O2 produced a concentration-dependent .OH as estimated by 2,3-DHBA and 2,5-DHBA. A standard curve was constructed for known concentrations of 2,3-DHBA and 2,5-DHBA against corresponding area under the peaks which then was used for measurement of 2,3-DHBA and 2,5-DHBA generated by UV irradiation of H2O2 in the presence of salicylic acid. SDG in the concentration range of 25, 50, 100, 250, 500, 750, 1000 and 2000 micrograms/ml (36.4, 72.8, 145.6, 364.0, 728.0, 1092.0, 1456.0 and 2912.0 microM respectively) produced a concentration-dependent decrease in the formation of 2,3-DHBA and 2,5-DHBA, the inhibition being 4 and 4.65% respectively with 25 micrograms/ml (36.4 microM) and 82 and 74% respectively with 2000 micrograms/ml (2912.0 microM). The decrease in .OH-adduct products was due to scavenging of .OH and not by scavenging of formed 2,3-DHBA and 2,5-DHBA. SDG prevented the lipid peroxidation of liver homogenate in a concentration-dependent manner in the concentration range from 319.3-2554.4 microM. These results suggest that SDG scavenges .OH and therefore has an antioxidant activity.
Mol Cell Biochem 1997 Mar
PMID:Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed. 906

The expression of two closely related peroxidase isogenes, Shpx6a and Shpx6b, of the legume Stylosanthes humilis was studied using isogene-specific reverse transcriptase PCR techniques. Results indicated that transcripts of both genes were rapidly induced following inoculation with the fungal pathogen Colletotrichum gloeosporioides, wounding and treatment with the defense regulator methyl jasmonate (MeJA). In contrast treatment of leaves of S. humilis with abscisic acid (ABA) and salicylic acid (SA) did not induce transcripts of either isogene. A genomic clone containing the Shpx6b gene was isolated and 594 bp of 5' sequence upstream of the translation start was fused in frame to the coding region of the uidA reporter gene and introduced into tobacco. Expression from the Shpx6b promoter in transgenic plants was determined by histochemical staining and quantitative assays of beta-glucuronidase (GUS). In transgenic tobacco, GUS expression was detected in cotyledons, vascular cells of young leaves, anthers, pollen, and the stigma and style. Wounding of the tobacco plants produced very localized GUS staining. Much more extensive staining for GUS was observed following inoculation of tobacco leaves with conidia of the fungal pathogen Cercospora nicotianae and the inoculation of wound sites with mycelium of the Oomycete pathogen Phytophthora parasitica var. nicotianae. Treatment of mature leaves with methyl jasmonate induced GUS activity while treatment with ABA, SA, and H2O2 had no effect. A similar strong induction of GUS activity was measured in young transgenic seedlings germinated on MeJA while some, but much weaker, induction of GUS activity was observed in seedlings treated with SA. The sequence of the promoter contained motifs homologous to putative cis elements in other plant genes responsive to MeJA. The Shpx6b gene is the first plant peroxidase gene shown to be induced by both microbial pathogens and MeJA and its promoter will be useful for investigations of signaling processes during fungal infection and for the expression of foreign gene products at infection sites.
Mol Plant Microbe Interact 1997 Apr
PMID:A peroxidase gene promoter induced by phytopathogens and methyl jasmonate in transgenic plants. 910 Mar 78

Acetylsalicylic acid (aspirin) is the drug most commonly self-administered to reduce inflammation, swelling, and pain. The established mechanism of action of aspirin is inhibition of the enzyme cyclo-oxygenase (COX). Once taken, aspirin is rapidly deacetylated to form salicylic acid, which may account, at least in part, for the therapeutic actions of aspirin. However, where tested, salicylic acid has been found to be a relatively inactive inhibitor of COX activity in vitro, despite being an effective inhibitor of prostanoids formed at the site of inflammation in vivo. Recently, the identification of a cytokine-inducible isoform of COX, COX-2, has led to the suggestion that salicylate produces its anti-inflammatory actions by inhibiting COX-2 induction through actions on nuclear factor kappaB (NF-kappaB). We have used interleukin 1beta-induced COX-2 in human A549 cells to investigate the mechanism of action of salicylate on COX-2 activity. Sodium salicylate inhibited prostaglandin E2 release when added together with interleukin 1beta for 24 hr with an IC50 value of 5 microg/ml, an effect that was independent of NF-kappaB activation or COX-2 transcription or translation. Sodium salicylate acutely (30 min) also caused a concentration-dependent inhibition of COX-2 activity measured in the presence of 0, 1, or 10 microM exogenous arachidonic acid. In contrast, when exogenous arachidonic acid was increased to 30 microM, sodium salicylate was a very weak inhibitor of COX-2 activity with an IC50 of >100 microg/ml. Thus, sodium salicylate is an effective inhibitor of COX-2 activity at concentrations far below those required to inhibit NF-kappaB (20 mg/ml) activation and is easily displaced by arachidonic acid.
Mol Pharmacol 1997 Jun
PMID:Sodium salicylate inhibits cyclo-oxygenase-2 activity independently of transcription factor (nuclear factor kappaB) activation: role of arachidonic acid. 918 56

In many interactions of plants with pathogens, the primary host defense reaction is accompanied by plant cell death at the site of infection. The resulting lesions are correlated with the establishment of an inducible resistance in plants called systemic acquired resistance (SAR), for which salicylic acid (SA) accumulation is a critical signaling event in Arabidopsis and tobacco. In Arabidopsis, the lesions simulating disease (lsd) mutants spontaneously develop lesions in the absence of pathogen infection. Furthermore, lsd mutants express SAR marker genes when lesions are present and are resistant to the same spectrum of pathogens as plants activated for SAR by necrogenic pathogen infection. To assess the epistatic relationship between SA accumulation and cell death, transgenic Arabidopsis unable to accumulate SA due to the expression of the salicylate hydroxylase (nahG) gene were used in crosses with the dominant mutants lsd2 or lsd4. Progeny from the crosses were inhibited for SAR gene expression and disease resistance. However, these progeny retained the spontaneous cell death phenotype similar to siblings not expressing nahG. Because lesions form in the absence of SA accumulation for isd2 and lsd4, a model is suggested in which lesion formation in these two mutants is determined prior to SA accumulation in SAR signal transduction. By contrast, the loss of SAR gene expression and disease resistance in nahG-expressing lsd mutants indicates that these traits are dependent upon SA accumulation in the SAR signal transduction pathway.
Mol Plant Microbe Interact 1997 Jul
PMID:Salicylate-independent lesion formation in Arabidopsis lsd mutants. 920 59

Pathogenesis-related (PR) proteins form a heterogeneous family of plant proteins that are likely to be involved in defense and are inducible by pathogen attacks. One group of PRs, represented by the subfamily PR-1, are low-molecular-weight proteins of unknown biochemical function. Here we describe the cloning and characterization of two closely related genes encoding a basic and an acidic PR-1 protein (PR1b1 and PR1a2) from tomato (Lycopersicon esculentum). We present a comparative study of the mode of transcriptional regulation of these two genes in transgenic tobacco plants using a series of promoter-GUS fusions. Unexpectedly, the chimeric PR1a2/GUS gene is not induced by pathogenic signals but instead shows constitutive expression with a reproducible developmental expression pattern. It is expressed in shoot meristems, trichomes, and cortical cells as well as in vascular and nearby tissues of the mature stem. This constitutive expression pattern may represent preemption of plant defenses against potential pathogens. Conversely, the chimeric PR1b1/GUS gene does not show any constitutive expression in the plant, but it is transcriptionally activated following pathogen attack. Upon infection by tobacco mosaic virus, the PR1b1 gene is strongly activated locally in tissues undergoing the hypersensitive response but not systemically in uninoculated tissues. Furthermore, its expression is induced by both salicylic acid and ethylene precursors, two signals that coexist and apparently mediate the activation of local defenses during the hypersensitive response. We speculate that the different mode of expression of the two genes presented here, together with that reported previously for the induction of other PR-1 genes in systemic, uninoculated tissues, may all be complementary and necessary for the plant to acquire an efficient refractory state to resist pathogen attacks.
Mol Plant Microbe Interact 1997 Jul
PMID:Two PR-1 genes from tomato are differentially regulated and reveal a novel mode of expression for a pathogenesis-related gene during the hypersensitive response and development. 920 67

The lesion-mimic mutants of certain plants display necrotic lesions resembling those of the hypersensitive response and activate local and systemic defense responses in the absence of pathogens. We have engineered a lesion-mimic phenotype in transgenic Russet Burbank potato plants through constitutive expression of a bacterio-opsin (bO) proton pump derived from Halobacterium halobium. Transgenic potato plants exhibiting a lesion-mimic phenotype had increased levels of salicylic acid and overexpressed several pathogenesis-related messenger RNAs, all hallmarks of systemic acquired resistance (SAR). The lesion-mimic plants also displayed enhanced resistance to the US1 isolate (A1 mating type) of a fungal pathogen, Phytophthora infestans, a causal agent of late blight disease. In contrast, little resistance was observed against the US8 isolate (A2 mating type) of this pathogen. Furthermore, a majority of the transgenic plants displaying the lesion-mimic phenotype had increased susceptibility to potato virus X. The tubers of these plants were not resistant to the bacterial pathogen Erwinia carotovora. These results indicate that expression of bO can result in the activation of defense responses in transgenic potato plants and show for the first time that bO expression can confer resistance to a pathogenic fungus. However, our results also demonstrate that like SAR, this "engineered" resistance is likely to be limited to certain pathogens and particular cultivars.
Mol Plant Microbe Interact 1997 Jul
PMID:Characterization of acquired resistance in lesion-mimic transgenic potato expressing bacterio-opsin. 920 68

Selected nonpathogenic, root-colonizing bacteria are able to elicit induced systemic resistance (ISR) in plants. To elucidate the molecular mechanisms underlying this type of systemic resistance, an Arabidopsis-based model system was developed in which Pseudomonas syringae pv. tomato and Fusarium oxysporum f. sp. raphani were used as challenging pathogens. In Arabidopsis thaliana ecotypes Columbia and Landsberg erecta, colonization of the rhizosphere by P. fluorescens strain WCS417r induced systemic resistance against both pathogens. In contrast, ecotype RLD did not respond to WCS417r treatment, whereas all three ecotypes expressed systemic acquired resistance upon treatment with salicylic acid (SA). P. fluorescens strain WCS374r, previously shown to induce ISR in radish, did not elicit ISR in Arabidopsis. The opposite was found for P. putida strain WCS358r, which induced ISR in Arabidopsis but not in radish. These results demonstrate that rhizosphere pseudomonads are differentially active in eliciting ISR in related plant species. The outer membrane lipopolysaccharide (LPS) of WCS417r is the main ISR-inducing determinant in radish and carnation, and LPS-containing cell walls also elicit ISR in Arabidopsis. However, mutant WCS417rOA-, lacking the O-antigenic side chain of the LPS, induced levels of protection similar to those induced by wild-type WCS417r. This indicates that ISR-inducing bacteria produce more than a single factor that trigger ISR in Arabidopsis. Furthermore, WCS417r and WCS358r induced protection in both wild-type Arabidopsis and SA-nonaccumulating NahG plants without activating pathogenesis-related gene expression. This suggests that elicitation of an SA-independent signaling pathway is a characteristic feature of ISR-inducing biocontrol bacteria.
Mol Plant Microbe Interact 1997 Aug
PMID:Differential induction of systemic resistance in Arabidopsis by biocontrol bacteria. 924 33

Pathogenesis-related (PR)-5 proteins are a family of proteins that are induced by different phytopathogens in many plants and share significant sequence similarity with thaumatin. We isolated a complementary DNA (ATLP-3) encoding a PR5-like protein from Arabidopsis which is distinct from two other previously reported PR5 cDNAs from the same plant species. The predicted ATLP-3 protein with its amino-terminal signal sequence is 245 amino acids in length and is acidic with a pl of 4.8. The deduced amino acid sequence of ATLP-3 shows significant sequence similarity with PR5 and thaumatin-like proteins from Arabidopsis and other plants and contains a putative signal sequence at the amino-terminus. The expression of ATLP-3 and a related gene (ATLP-1) that we previously isolated from Arabidopsis was induced by pathogen infection and salicylic acid, a known inducer of pathogenesis-related genes. Southern blot analysis indicates that the ATLP-1 and ATLP-3 are coded by single-copy genes. To study the effect of ATLP-1 and ATLP-3 proteins on fungal growth, the cDNA regions corresponding to putative mature protein were expressed in Escherichia coli and the cDNA encoded proteins were purified. ATLP-1 and ATLP-3 proteins cross-reacted with anti-osmotin and anti-zeamatin antibodies. ATLP-3 protein showed antifungal activity against several fungal pathogens suggesting that ATLP-3 may be involved in plant defense against fungal pathogens.
Plant Mol Biol 1997 Aug
PMID:Cloning and expression of a PR5-like protein from Arabidopsis: inhibition of fungal growth by bacterially expressed protein. 929 Jun 46

Seven agents were analyzed with respect to their ability to induce heat shock protein (HSP) synthesis in C6 rat glioma cells. Induction of HSP synthesis was correlated with cytotoxicity and lipophilicity of the substances. In addition to the first four n-alcohols (methanol, ethanol, propanol and butanol) and phenol, whose capacity to induce HSP was analyzed earlier (Neuhaus-Steinmetz et al., 1994. Mol. Pharmacol. 45, 36-41), isopropanol, 1,4-dinitrophenol (DNP), diethylstilbestrol (DES), carbonylcyanide-m-chlorophenylhydrazone (CCCP), rotenone, paracetamol and acetyl salicylic acid (ASA) induced HSP synthesis after a 1-h incubation at a substance-specific concentration. The maximal induction of HSPs was closely correlated with the cytotoxicity of all substances and occurred when cell viability was reduced to 75 +/- 11% of the controls. Cytotoxicity and the ability to induce HSP were correlated with the lipophilicity of the alcohols, phenol, rotenone and paracetamol. Calculation of the hypothetical membrane concentrations of these compounds yielded a nearly equal value (0.54 +/- 0.13 M), indicating that interaction of substances with lipophilic cellular compounds, such as membranes or lipophilic core regions of proteins, is a critical step leading to HSP induction. This assumption is supported by a correlation between HSP induction and protein denaturation by the different alcohols (Herskovits et al., 1970. J. Biol. Chem. 245, 2588-2598). We assume that the amount of misfolded proteins induced by these lipophilic agents is responsible for the induction of HSP synthesis. ASA, DNP and CCCP induced HSP at lower concentrations than substances with a similar lipophilicity, which may be due to effects which add to the misfolding of proteins or to other signal pathways.
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PMID:Heat shock protein induction by certain chemical stressors is correlated with their cytotoxicity, lipophilicity and protein-denaturing capacity. 935 37

Menadione (vitamin K-3,2-methyl-1,4-naphthoquinone), a redox cycling reagent, generates reactive oxygen intermediates and causes oxidative injury. The addition of menadione to Hep G2 cells produced a time- and concentration-dependent loss of cell viability. Preincubation of Hep G2 cells with low, nontoxic concentrations of menadione increased the viability of the cells against toxic doses of menadione or H2O2. Maximum protection was found with menadione concentrations of approximately 3 microM and preincubation times of approximately 45 min. This protective effect could be blocked by the protein synthesis inhibitor cycloheximide and by a variety of antioxidants. The transcription factor nuclear factor-kappaF (NF-kappaB) is known to be activated by many compounds, including reactive oxygen intermediates. Menadione activated NF-kappaB as determined by electrophoretic mobility shift assays. This activation was prevented by the same antioxidants that blocked protection against cytotoxicity produced by preincubation with menadione. Anti-p50 IgG prevented the menadione-stimulated binding of NF-kappaB to the oligonucleotide probe, whereas anti-p65 IgG produced a supershift of the NF-kappaB/oligonucleotide complex. Salicylate prevented the activation of NF-kappaB by menadione, and under these conditions, salicylate potentiated the cytotoxicity of menadione or H2O2. Transfection with a plasmid containing cDNA encoding mouse IkappaBbeta, an inhibitor of NF-kappaB, resulted in increased toxicity by menadione. Furthermore, when protein kinase C was down-regulated by prolonged treatment with active phorbol ester (phorbol-12-myristate-13-acetate), the Hep G2 cells became more sensitive to menadione treatment. However, short term treatment with PMA, which activated NF-kappaB, resulted in protection against menadione cytotoxicity. Menadione cytotoxicity was enhanced when the Hep G2 cells were depleted of GSH. An increased level of GSH was observed after menadione pretreatment; this increase was blocked by salicylate, thereby linking the GSH increase to activation of NF-kappaB by menadione. The results of the current study suggest that menadione pretreatment protects Hep G2 cells from oxidative injury through an NF-kappaB-related mechanism, which may involve, in part, increased production of GSH.
Mol Pharmacol 1997 Oct
PMID:Menadione cytotoxicity to Hep G2 cells and protection by activation of nuclear factor-kappaB. 938 28


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