Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secretory type IIA phospholipase A(2) (sPLA(2)-IIA) is a critical enzyme involved in inflammatory diseases. We have previously identified alveolar macrophages (AMs) as the major pulmonary source of lipopolysaccharide (LPS)-induced sPLA(2)-IIA expression in a guinea pig model of acute lung injury (ALI). Here, we examined the role of arachidonic acid (AA) in the regulation of basal and LPS-induced sPLA(2)-IIA expression in AMs. We showed that both AA and its nonmetabolizable analog, 5,8,11,14-eicosatetraynoic acid (ETYA), inhibited sPLA(2)-IIA synthesis in unstimulated AMs. However, only AA inhibited sPLA(2)-IIA expression in LPS-stimulated cells, suggesting that this effect requires metabolic conversion of AA. Indeed, cyclooxygenase inhibitors abolished this down-regulation. Prostaglandins PGE(2), PGA(2), and 15d-PGJ(2) also inhibited the LPS-induced sPLA(2)-IIA expression. Nuclear factor-kappaB (NF-kappaB) was found to regulate sPLA(2)-IIA expression in AMs. Both AA and ETYA inhibited basal activation of NF-kappaB but had no effect on LPS-induced NF-kappaB translocation, suggesting that suppression of sPLA(2)-IIA synthesis by AA in LPS-stimulated cells occurs via a NF-kappaB-independent pathway. 15-Deoxy-Delta(12,14)-PGJ(2) and ciglitazone, which are, respectively, natural and synthetic ligands for peroxisome proliferator-activated receptor-gamma (PPAR-gamma), inhibited LPS-induced sPLA(2)-IIA synthesis, whereas PPAR-alpha ligands were ineffective. Moreover, electrophoretic mobility shift assay showed PPAR activation by AA and PPAR-gamma ligands in LPS-stimulated AMs. Our results suggest that the down-regulation of basal sPLA(2)-IIA expression is unrelated to the metabolic conversion of AA but is dependent on the impairment of NF-kappaB activation. In contrast, the inhibition of LPS-stimulated sPLA(2)-IIA expression is mediated by cyclooxygenase-derived metabolites of AA and involves a PPAR-gamma-dependent pathway. These findings provide new insights for the treatment of ALI.
Mol Pharmacol 2002 Apr
PMID:Arachidonic acid differentially affects basal and lipopolysaccharide-induced sPLA(2)-IIA expression in alveolar macrophages through NF-kappaB and PPAR-gamma-dependent pathways. 1190 Dec 17

We reported earlier that expression of Sox-4 was found to be elevated during prostaglandin (PG) A(2) and delta(12)-PGJ(2) induced apoptosis in human hepatocarcinoma Hep3B cells. In this study, the role of Sox-4 was examined using human Hep3B and HepG2 cell lines. Sox-4 induction by several apoptotic inducer such as A23187 (Ca(2+) ionophore) and etoposide (topoisomerase II inhibitor) and Sox-4 transfection into the cells were able to induce apoptosis as observed by the cellular DNA fragmentation. Antisense oligonucleotide of Sox-4 inhibited the induction of Sox-4 expression and blocked the formation of DNA fragmentation by PGA(2) and delta(12)-PGJ(2) in Hep3B and HepG2 cells. Sox-4-induced apoptosis was accompanied with caspase-1 activation indicating that caspase cascade was involved in this apoptotic pathway. These results indicate that Sox-4 is involved in Hep3B and HepG2 cells apoptosis as an important apoptotic mediator.
Exp Mol Med 2002 Jul 31
PMID:Sox-4 is a positive regulator of Hep3B and HepG2 cells' apoptosis induced by prostaglandin (PG)A(2) and delta(12)-PGJ(2). 1221 17

The production of pectinase, the major virulence determinant of soft-rot Erwinia species, is controlled by many regulatory factors. We focused on the major regulatory proteins, KdgR, CRP, Pir, and PecS, characterized mainly in E. chrysanthemi, and tested for their presence and function in the control of pectate lyase (Pel) and polygalacturonase (Peh) production in E. carotovora subsp. carotovora. Homologues of kdgR and crp but not of pir and pecS were detected by Southern blot analyses in E. carotovora subsp. carotovora. In fact, KdgR and CRP homologues of E. carotovora subsp. carotovora had high amino acid identities to those of E. chrysanthemi, including a complete match of the hypothetical helix-turn-helix DNA-binding motif. However, in Western blot analyses using anti-Pir (E. chrysanthemi) antibodies, a cross-reacting protein was present in both Erwinia species, although Pel production in E. carotovora subsp. carotovora was not further stimulated by adding plant extract into the medium containing PGA (polygalacturonic acid) in which hyperinduction by Pir has been reported in E. chrysanthemi EC16. When plasmids that contained each of these regulatory genes from E. chrysanthemi were introduced into E. carotovora subsp. carotovora, Pel production was controlled as predicted from their roles in E. chrysanthemi, except for PecS. PecS exerted a positive control in E. carotovora subsp. carotovora, in contrast to a negative control in E. chrysanthemi. DNA-binding assays demonstrated that KdgR, CRP, Pir, and PecS of E. chrysanthemi and KdgR and CRP homologues of E. carotovora subsp. carotovora could bind to the promoter regions of pel-1, pel-3, and peh of E. carotovora subsp. carotovora. Taken together, KdgR and CRP homologues of E. carotovora subsp. carotovora may regulate Pel and Peh production as in E. chrysanthemi. However, the presence of Pir and PecS homologues in E. carotovora subsp. carotovora was not identified in this study, though these proteins of E. chrysanthemi were functional on the promoter regions of the pectinase genes of E. carotovora subsp. carotovora.
Mol Plant Microbe Interact 2003 Mar
PMID:Comparative study of regulatory mechanisms for pectinase production by Erwinia carotovora subsp. carotovora and Erwinia chrysanthemi. 1265 Apr 54

Cyclopentenone prostaglandins (CyPGs), derivatives of arachidonic acid, have been suggested to exert growth-inhibitory activity through peroxisome proliferator-activated receptor (PPAR)-dependent and -independent mechanisms. Here we examined various eicosanoids for growth inhibition and found that the terminal derivative of prostaglandin (PG) J(2) metabolism, 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), and PGA(1) markedly inhibited the growth and induced apoptosis in AGS gastric carcinoma cells. There were no significant increases in cell death and DNA-fragmentation in the cells with overexpression of PPARalpha or PPARgamma, indicating the possibility that 15d-PGJ(2) and PGA(1) induced apoptosis through PPAR-independent pathway. Moreover, 15d-PGJ(2) and PGA(1) activated the c-jun N-terminal kinase (JNK) and caspase-3 activity in dose- and time-dependent manners. To examine further the role of JNK signaling cascades in apoptosis induced by 15d-PGJ(2) and PGA(1), we transfected dominant-negative (DN) mutants of JNK plasmid into the cells to analyze the apoptotic characteristics of cells overexpressing DN-JNK following exposure to 15d-PGJ(2) and PGA(1). Overexpression of DN-JNK significantly repressed both endogenous JNK and caspase-3 activity, and subsequently decreased apoptosis induced by 15d-PGJ(2) and PGA(1). These results suggested that CyPGs, such as 15d-PGJ(2) and PGA(1), activated JNK signaling pathway, and that JNK activation may be involved in 15d-PGJ(2)- and PGA(1)-induced apoptosis.
Mol Carcinog 2003 May
PMID:Involvement of c-jun N-terminal kinase activation in 15-deoxy-delta12,14-prostaglandin J2-and prostaglandin A1-induced apoptosis in AGS gastric epithelial cells. 1272 Feb 96

The interaction between fungal endopolygalacturonases (EPGs) and polygalacturonase-inhibiting proteins (PGIPs) found in plant cell walls has been well established. The typical EPG/PGIP interaction is characterized by high affinity, reversibility, and a 1:1 stoichiometry that results in lowering the catalytic rate of a particular endopolygalacturonase by up to 99.7%. Various EPG and PGIP isoforms and glycoforms have been isolated and characterized, and combinations of EPGs and PGIPs demonstrate a range of enzyme inhibition. EPG/PGIP interactions have prompted many researchers to suspect the involvement of these proteins in the production of specific signals (oligosaccharins) during plant pathogenesis. We have recently reported on initial studies in our laboratory indicating that, for certain EPG/PGIP combinations, the specific activity of EPG is increased beyond that characteristic of the enzyme alone. In this paper, we present a detailed analysis of the product of the interaction of native Phaseolus vulgaris PGIP-2 with five EPGs from Aspergillus niger, namely PGI, PGII, PGA, PGB, and PGC in the presence of homogalacturonan. We demonstrate that for PGA and PGC, the interaction with PGIP-2 may result in either inhibition or activation in a manner that is pH dependent. This data suggests the need for a reevaluation of the conventional description applied to PGIPs; suggestions include polygalacturonase-binding protein and polygalacturonase-modulating protein.
Mol Plant Microbe Interact 2004 Aug
PMID:Polygalacturonase-inhibiting proteins can function as activators of polygalacturonase. 1530 10

Bacteria in a biofilm are enmeshed in a self-synthesized extracellular polysaccharide matrix that holds the bacteria together in a mass and firmly attaches the bacterial mass to the underlying surface. A major component of the extracellular polysaccharide matrix in several phylogenetically diverse bacteria is PGA, a linear polymer of N-acetylglucosamine residues in beta(1,6)-linkage. PGA is produced by the Gram-negative periodontopathogen Actinobacillus actinomycetemcomitans as well as by the Gram-positive device-associated pathogen Staphylococcus epidermidis. We recently reported that A.actinomycetemcomitans produces a soluble glycoside hydrolase named dispersin B, which degrades PGA. Here, we present the crystal structure of dispersin B at 2.0A in complex with a glycerol and an acetate ion at the active site. The enzyme crystallizes in the orthorhombic space group C222(1) with cell dimensions a=41.02A, b=86.13A, c=185.77A. The core of the enzyme consists a (beta/alpha)(8) barrel topology similar to other beta-hexosaminidases but significant differences exist in the arrangement of loops hovering in the vicinity of the active site. The location and interactions of the glycerol and acetate moieties in conjunction with the sequence analysis suggest that dispersin B cleaves beta(1,6)-linked N-acetylglucosamine polymer using a catalytic machinery similar to other family 20 hexosaminidases which cleave beta(1,4)-linked N-acetylglucosamine residues.
J Mol Biol 2005 Jun 10
PMID:Structural analysis of dispersin B, a biofilm-releasing glycoside hydrolase from the periodontopathogen Actinobacillus actinomycetemcomitans. 1587 75

The RNA-binding protein CsrA represses biofilm formation, while the non-coding RNAs CsrB and CsrC activate this process by sequestering CsrA. We now provide evidence that the pgaABCD transcript, required for the synthesis of the polysaccharide adhesin PGA (poly-beta-1,6-N-acetyl-d-glucosamine) of Escherichia coli, is the key target of biofilm regulation by CsrA. csrA disruption causes an approximately threefold increase in PGA production and an approximately sevenfold increase in expression of a pgaA'-'lacZ translational fusion. A DeltacsrBDeltacsrC mutant exhibits a modest decrease in pgaA'-'lacZ expression, while the response regulator UvrY, a transcriptional activator of csrB and csrC, stimulates this expression. Biofilm formation is not regulated by csrA, csrB or uvrY in a DeltapgaC mutant, which cannot synthesize PGA. Gel mobility shift and toeprint analyses demonstrate that CsrA binds cooperatively to pgaA mRNA and competes with 30S ribosome subunit for binding. CsrA destabilizes the pgaA transcript in vivo. RNA footprinting and boundary analyses identify six apparent CsrA binding sites in the pgaA mRNA leader, the most extensive arrangement of such sites in any mRNA examined to date. Substitution mutations in CsrA binding sites overlapping the Shine-Dalgarno sequence and initiation codon partially relieve repression by CsrA. These studies define the crucial mechanisms, though not the only means, by which the Csr system influences biofilm formation.
Mol Microbiol 2005 Jun
PMID:CsrA post-transcriptionally represses pgaABCD, responsible for synthesis of a biofilm polysaccharide adhesin of Escherichia coli. 1591 13

Lactoferrin is a metal-binding glycoprotein exhibiting multifunctional immunoregulation of antibacterial, antioxidant, anti-endotoxin and antiviral activities. Uptake of porcine lactoferrin (PLF) has been shown to enhance resistance to diarrhea and anemia in neonatal piglets. In this study, the methylotrophic yeast, Pichia pastoris, was used to express a recombinant PLF (rPLF) gene from swine mammary gland. A synthetic secretion cassette was constructed using the inducible promoter of the alcohol oxidase-1 gene (AOX1) and the yeast alpha-mating factor signal peptide. After electroporation and Zeocin selection, several clones expressed high levels of rPLF protein which constitutes more than 30% of the total protein. A time-course study showed that rPLF mRNA transcripts are stably expressed during 120 h of culture induction. rPLF was exported into the culture supernatant at approximately 87 mg/l and a large portion of rPLF was accumulated in the cell cytoplasm at approximately 760 mg/l after 72 h of methanol induction. Recombinant PLF protein was purified via a heparin column using a fast protein liquid chromatography system. The glycosylation of P. pastoris-derived rPLF was analyzed and similar patterns to milk PLF were observed. Pepsin hydrolysate of rPLF displayed high bactericidal activity against Escherichia coli ATCC 25922 under scanning electron microscopy observation and minimal inhibitory concentration and minimal bactericidal concentration tests. Our results suggested that the methylotrophic yeast-inducible system is suitable for large-scale production of active antibacterial rPLF glycoprotein.
J Mol Microbiol Biotechnol 2004
PMID:Production of recombinant porcine lactoferrin exhibiting antibacterial activity in methylotrophic yeast, Pichia pastoris. 1608 16

Biofilms are communities of microbial cells that are encased in a self-produced, polymeric matrix and are adherent to a surface. For several species of bacteria, an enhanced ability to form biofilms has been linked with an increased capability to produce exopolymers. To identify exopolymers of Bacillus subtilis that can contribute to biofilm formation, we transferred the genetic determinants that control exopolymer production from a wild, exopolymer-positive strain to a domesticated, exopolymer-negative strain. Mapping these genetic determinants led to the identification of gamma-poly-dl-glutamic acid (gamma-PGA) as an exopolymer that increases biofilm formation, possibly through enhancing cell-surface interactions. Production of gamma-PGA by Bacillus subtilis was known to be dependent on the two-component regulator ComPA; this study highlighted the additional dependence on the DegS-DegU, DegQ and SwrA regulator proteins. The inability of the domestic strain of B. subtilis to produce gamma-PGA was mapped to two base pairs; a single base pair change in the promoter region of degQ and a single base pair insertion in the coding region of swrA. Introduction of alleles of degQ and swrA from the wild strain into the domestic strain was sufficient to allow gamma-PGA production. In addition to controlling gamma-PGA production, ComPA and DegSU were also shown to activate biofilm formation through an as yet undefined pathway. The identification of these regulators as affecting gamma-PGA production and biofilm formation suggests that these processes are regulated by osmolarity, high cell density and phase variation.
Mol Microbiol 2005 Aug
PMID:Defining the genetic differences between wild and domestic strains of Bacillus subtilis that affect poly-gamma-dl-glutamic acid production and biofilm formation. 1609 Oct 50

Maternal diabetes significantly increases the risk of congenital malformations, and the mechanisms involved are not yet clarified. This study was designed to address peroxisome proliferator-activated receptor delta (PPARdelta) involvement in diabetic embryopathy. We investigated the concentrations of PPARdelta and its endogenous agonist prostaglandin (PG)I(2), as well as the effect of PPARdelta activation on lipid metabolism and PGE(2) concentrations in embryos from control and streptozotocin-induced diabetic rats during early organogenesis. Embryos from diabetic rats showed decreased concentrations of PPARdelta and its endogenous agonist PGI(2) when compared with controls. In embryos from control rats, the addition of the PPARdelta activators (cPGI(2) and PGA(1)) increased embryonic phospholipid levels and de novo phospholipid synthesis studied using (14)C-acetate as a tracer. PGE(2) formed from arachidonate released from phospholipid stores was also up-regulated by PPARdelta activators. In embryos from diabetic rats, reduced phospholipid synthesis and PGE(2) content were observed, and clearly up-regulated by cPGI(2) additions to values similar to those found in control embryos. These data suggest that PPARdelta may play an important role in lipid metabolic and signalling pathways during embryo organogenesis, developmental pathways that are altered in embryos from diabetic rats, possibly as a result of a reduction in levels of PPARdelta and its endogenous activator PGI(2).
Mol Hum Reprod 2007 Feb
PMID:PPARdelta and its activator PGI2 are reduced in diabetic embryopathy: involvement of PPARdelta activation in lipid metabolic and signalling pathways in rat embryo early organogenesis. 1714 78


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