Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Larvae of the tobacco hornworm, Manduca sexta, respond to intrahemocoelic injection of bacteria or bacterial cell wall peptidoglycan with induced synthesis of a suite of antibacterial proteins. Previous studies have demonstrated peptidoglycan regulation of the synthesis of these antibacterial proteins. In addition to eliciting enhanced synthesis of antibacterial proteins, peptidoglycan fragments also elicit a "malaise syndrome" characterized by decreased feeding and growth, delayed metamorphosis, and altered excretion. We speculate that these symptoms may be components of a mechanism to flush out and sterilize the midgut lumen, one of the primary sources of bacterial infection in insects. Studies of naive larvae have demonstrated the accumulation of lysozyme in the differentiating pupal midgut epithelium and release of lysozyme into the pupal midgut lumen after the larval midgut epithelium has been sloughed off. These observations have been extended by the identification of potent bactericidal activity against E. coli and immunoreactive hemolin, together with lysozyme, in the lumen of the newly differentiated pupal midgut.
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PMID:Regulation of antibacterial protein synthesis following infection and during metamorphosis of Manduca sexta. 819 26

The immune state of insects is defined by a set of proteins that is absent in the naive state. To explore the immune system of Trichoplusia ni in more detail we have employed a PCR differential display technique to compare the mRNA population of untreated last instar larvae to that of immunized animals. In the primary display, more than one hundred bands seemed induced upon bacterial challenge. When they were used as probes in Northern blots, 35% of these probes detected inducible mRNA species. Such probes were used to screen a cDNA library from immunized larvae. We isolated clones for T. ni homologs of cecropin A, lysozyme and attacin. One differentially expressed band hybridized to clones for BJHSP1, a hemacy-anin-related protein which is hormonally up-regulated in last instar larvae; this induction is probably not related to the bacterial infection. Still other probes recognized inducible mRNAs of 1.6 and 1.0 kb. The corresponding cDNA clones did not show strong sequence homology to any known proteins. We have demonstrated the potential of this PCR technique to display both known and unknown genes specific for the immune state of whole insects against a background of genes involved in larval development.
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PMID:PCR differential display of immune gene expression in Trichoplusia ni. 888 60

A genomic DNA sequence encoding a basic lysozyme was isolated from the malaria vector mosquito Anopheles gambiae by screening a library with a probe prepared by PCR of reverse transcribed adult RNA. The sequence consists of an upstream region of about 2 kb, a coding region containing three exons and two introns, and a short 3' untranslated region. The coding region indicates that this mosquito lysozyme consists of a signal peptide of 20 residues followed by an 120 aa mature protein which is very similar to other basic lysozymes. The two small introns, 67 and 76 bp, are located at evolutionarily conserved sites. RT-PCR indicated that this gene is expressed abundantly in sugar-fed adults, and at considerably lower levels when females have fed on blood. Although it remains to be seen whether this gene is induced by bacterial infection, the surrounding sequence contains six sequence motifs very similar to the consensus binding sites for a transcription factor similar to NF-kappa B that are found associated with most insect immune response genes. This lysozyme gene maps to division 27 on the left arm of polytene chromosome 2L. An ORF unrelated to any animal protein in current data bases was found at the 5' end of the clone.
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PMID:Analysis of a lysozyme gene from the malaria vector mosquito, Anopheles gambiae. 889 Jul 41

A cDNA encoding a lysozyme expressed specifically in the salivary glands of the malaria vector mosquito, Anopheles darlingi, was isolated by differential screening an adult female salivary gland library with abdomen and salivary gland cDNAs. The primary nucleic acid sequence of the cDNA contains a deduced coding region of 429 nucleotides and 5'- and 3'-end non-transcribed regions. A signal peptide of twenty-three amino acids and a mature protein of 120 amino acids are evident in the conceptual translation product. The results of RT-PCR experiments indicated that in adult mosquitoes this gene is expressed specifically in the salivary glands. Lysozyme enzymatic activity was detected in the salivary glands and abdomens of adult mosquitoes, but the pH optimum differed for each tissue and this was interpreted to indicate the presence of more than one enzyme, each being expressed in a different tissue. The salivary gland lysozyme may be involved in protection against bacterial infection in the anterior portion of the mosquito digestive tract.
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PMID:A lysozyme in the salivary glands of the malaria vector Anopheles darlingi. 966 75

Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models, and interleukin (IL)-1beta, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-alpha) are recognized as being important local mediators in acute inflammation. We characterized middle ear inflammatory responses in the chinchilla otitis media model after injecting a very small number of viable pneumococci into the middle ear, similar to the natural course of infection. Middle ear fluid (MEF) concentrations of IL-1beta, IL-6, IL-8, and TNF-alpha were measured by using anti-human cytokine enzyme-linked immunosorbent assay reagents. IL-1beta showed the earliest peak, at 6 h after inoculation, whereas IL-6, IL-8, and TNF-alpha concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8, and TNF-alpha but not IL-1beta concentrations correlated significantly with total inflammatory cell numbers in MEF, and all four cytokines correlated significantly with MEF neutrophil concentration. Several intercytokine correlations were significant. Cytokines, therefore, participate in the early middle ear inflammatory response to S. pneumoniae.
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PMID:Middle ear fluid cytokine and inflammatory cell kinetics in the chinchilla otitis media model. 1008 40

Extracts from both the vitelline envelope (VE) and fertilisation envelopes (FE) of rainbow trout eggs have the ability to exert a bactericidal effect on Gram-positive and -negative bacteria. The effect may be due to the presence of phospholipase D (PLD), lysozyme, proteinase and DNases, as the extracts contain these enzyme activities. The intensity of chorionic PLD and lysozyme activities in the VE extract was maintained in the FE without any alteration in activity even after transformation in the course of the cortical reaction, as components of a fundamental architecture of the envelope. Both extracts also contain different types of proteinase activities. Treatment with VE or FE extract seriously damaged the outer membrane of Gram-negative bacteria and the plasma membrane of Gram-positive and -negative bacteria at the ultrastructural level. Chorionic DNases probably degrade DNA of bacterial cells killed by virtue of the action of PLD and/or lysozyme and contribute to the transmigration of nucleosides and/or nucleotides produced by degrading bacterial DNA after degradation of bacterial components by the actions of the chorionic PLD, lysozyme and proteinase. These results suggest that the bactericidal process manifested by the VE or FE extract may start with the action of PLD and/or lysozyme against bacteria and be completed by subsequent degradation of constitutive proteins and DNA by the action of proteinases and DNases, respectively. Thus the VE and FE are able to protect the egg itself and the embryo, respectively, from bacterial infection in the internal or external environments.
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PMID:Enzymes responsible for the bactericidal effect in extracts of vitelline and fertilisation envelopes of rainbow trout eggs. 1101 5

Lysozyme is secreted in large quantities in human airways (10-20 mg/day), where it helps to defend against bacterial and fungal infection. Lysozyme expression is restricted to the serous cells of the submucosal glands, which also express high levels of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. It is often assumed that mucus secretion in human airways is coupled to anion secretion through CFTR Cl(-) channels located in the apical membrane. Therefore, a defect in CFTR function could cause abnormal mucus secretion leading to persistent bacterial infection and inflammation of the airways. In this study we measured simultaneous secretion of lysozyme and Cl(-) from human airway epithelial serous cells. Secretion of lysozyme was measured by a turbidimetric assay that relies on the ability of lysozyme to disrupt the wall of the bacterium Micrococcus lysodeikticus, thus causing a fall in the optical density of the sample. Secretion of Cl(-) was measured as short-circuit current in a modified Ussing chamber. Activation of Cl(-) secretion by stimulation of cAMP- or Ca(2+)-dependent pathways caused comparable increases in lysozyme secretion. Similarly, blockers of Cl(-) secretion, such as diphenylamine-2-carboxylate (DPC), also reduced lysozyme secretion. However, while treatment of airway submucosal gland cells with antisense oligonucleotides directed against CFTR reduced Cl(-) secretion, it had no significant effect on the total amount of lysozyme secretion. These results suggest a role for functional CFTR in regulation of lysozyme secretion in human airways.
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PMID:CFTR and lysozyme secretion in human airway epithelial cells. 1184 2

Polychlorinated biphenyls (PCBs) are industrial chemicals which have been released into the environment resulting in widespread and persistent contamination. PCBs exist as 209 different congeners depending on the chlorine substitution on the biphenyl rings; the physical properties and the toxic effects of a PCB congener are structure-dependent. In this work, individual ortho-substituted non coplanar PCB congeners were tested for their effects on the function of mussel (Mytilus galloprovincialis Lam.) hemocytes. Moreover, the possibility that in mussel hemocytes different PCBs may affect the signal transduction pathways involved in the immune response was investigated, with particular regards to relevant components of tyrosine-kinase mediated cell signaling. The results were compared with those obtained with a model of non-ortho-substituted coplanar congener. The results demonstrate that the di-ortho-substituted, non coplanar PCB congeners P47 (2,2',4,4'-tetrachlorobiphenyl) and P153 (2,2',4,4',5,5'-hexachlorobiphenyl) can alter immune parameters of mussel hemocytes, such as microbicidal activity and lysosomal enzyme release, respectively. Both congeners, as well as the non-ortho, coplanar congener P77 (3,3',4,4'-tetrachlorobiphenyl) significantly reduced hemocyte lysosomal membrane stability; however, P77 had no effect on either bacterial killing or lysozyme release. P47, P153 and P77 affected different components of tyrosine kinase-mediated cell signalling; in particular, they lead to a time-dependent increase in the phosphorylation level of the stress activated p38 and JNK Mitogen Activated Protein Kinases (MAPKs), as evaluated by Western blotting of hemocyte protein extracts with specific anti-phospho-MAPK antibodies. P153 also increased the level of phosphorylated ERK (extracellularly regulated) MAPKs. Moreover, non coplanar P47 and P153 caused increased tyrosine phosphorylation of the transcription factor STAT5, thus possibly affecting gene expression, whereas coplanar P77 was ineffective. The results demonstrate that MAPKs, and in particular the stress-activated p38 and JNK MAPKs, that represents a key step in the response of mussel hemocytes to bacterial infection, are a target for different non coplanar and coplanar PCB congeners. The results also show functional differences between different PCB congeners with respect to the hemocyte functions. However, chlorine substitution at the ortho positions is not necessarily related to immunotoxicity: the hexachlorinated P128 (2,2',3,3',4,4'-hexachlorobiphenyl) had no significant effect on mussel hemocytes, whereas its isomer P153, that represents a major component of environmental PCBs, and that is accumulated in mussel tissues, significantly affected both aspects of the immune response and relevant signal transduction pathways. These are the first data on the effects and possible mechanisms of immunotoxicity of non coplanar PCBs in mussel hemocytes. The results support the hypothesis that the innate immune system is a sensitive target for these contaminants in both vertebrates and invertebrates. Moreover, when considering that non coplanar congeners are present both in commercial mixtures and, in higher proportions, in environmental samples, the results suggest that bivalve hemocytes represent a useful model for evaluating the potential immunotoxicity of PCB contamination.
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PMID:Effects of PCB congeners on the immune function of Mytilus hemocytes: alterations of tyrosine kinase-mediated cell signaling. 1271 18

New cysteine protease inhibitors in human tears and milk and their medical significance are reviewed in this paper. As protective components against bacterial infection in the eyes, we detected four kinds of anti-bacterial proteins in normal human tears including lysozyme and three kinds of cysteine protease inhibitors. Using our reverse zymography of normal tears, three kinds of cysteine protease inhibitors were found to be 78kDa, 20kDa and 15kDa and were determined to be lactoferrin, Von Ebner's Gland (VEG) protein and cystatin S, respectively. All of them belong to the cystatin super family and VEG protein and cystatin S are well known cysteine protease inhibitors. The C-terminus area 17mer peptide, Y679-K695, of lactoferrin showed strong homology with a common active domain of the cystatin family and the synthesized peptide showed inhibition of cysteine proteases. Not only were disease-specific changes found in these inhibitor profiles, but also disease-specific new inhibitors in patients tears with certain autoimmune diseases. A 35kDa inhibitor, which was detected specifically in tears with Behcet's disease, an typical autoimmune disease, was determined to be a lacrimal acidic proline-rich protein based on the N-terminus sequence analysis. A 65kDa inhibitor of tears with Harada's autoimmune disease was determined to be an Ig heavy chain V-III region. In addition, lactoferrin content in Harada's disease was very low. We found two cathepsin inhibitors in bovine milk using reverse zymography, namely lactoferrin and beta-casein. The L133-Q151, in the human beta-casein molecule is the active inhibitory domain. They may play an important role in antiseptic and anti-infectious functions.
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PMID:Medical significance of cysteine protease inhibitors in mammalian secretory fluids. 1367 84

Lysozyme protects us from the ever-present danger of bacterial infection. The expression of lysozyme is, in part, regulated by the Ets factor, myeloid elf-1-like factor (MEF). MEF binds to the ETS site of the lysozyme promoter at -46 to -40bp. Closer analysis of the promoter using a series of deletion mutants and point mutants indicated that the region around -75bp is also essential in regulating the activity of lysozyme. The sequences in this region correspond to the Sp1 consensus binding site. Sp1 is known to regulate a variety of house-keeping and tissue-specific genes by itself or with other transcription factors like AP-1 or ETS. We indicate here that Sp1 regulates the lysozyme gene by binding to the GT-core sequences of lysozyme promoter. Treatment with mithramycin A down-regulated the promoter activity and the transfection of anti-sense Sp1 induced a decrease in the endogenous expression of lysozyme.
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PMID:Sp1 is involved in the transcriptional activation of lysozyme in epithelial cells. 1550 56


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