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)

Serum amyloid protein (SAA) appears to be the precursor of amyloid protein AA, the non-immunoglobulin fibril protein of secondary amyloidosis. Since amyloidosis is known to occur in high frequency associated with lepromatous leprosy (LL), we have examined the SAA levels in untreated LL patients and compared them to the levels observed in patients with tuberculoid leprosy (TT) and a large number observed in healthy controls. We found that SAA is markedly elevated in LL when compared to TT and controls. No clear correlation could be established with C-reactive protein, a well-documented acute phase reactant, or serum lysozyme levels that reflect the presence of monocyte activity. This study showed that SAA levels in leprosy do not appear to be a reflection of inflammatory activity or monocyte turnover. Whether amyloidosis will be more prevalent in patients who have higher SAA levels remains to be determined.
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PMID:Serum amyloid protein SAA, C-reactive protein and lysozyme in leprosy. 57 49

Evidence implicates cells belonging to the mononuclear phagocytic system (MPS) in the development of some forms of amyloidosis (10, 22). Whether or not the MPS is involved in central nervous system amyloidosis is not known. As a first step to address this issue, microglial and astroglial cells isolated from mouse brains were cultured and characterized as to the properties they may share with other members of the MPS. It was shown by light and electron microscopy that both cell types phagocytose latex particles, but that only microglial cells engulf immunoglobulin sensitized erythrocytes. By means of immunohistochemical, immunofluorescence, and immunoblotting techniques, it was established that the cells contain and secrete lysozyme as well as the proteinase inhibitor cystatin-C (-gamma trace). Cystatin-C was distributed in the cytoplasm and the nucleus and was strikingly associated with filaments and bundles of fibrils. Another enzyme, commonly used to distinguish cells belonging to the MPS, is alpha-naphthyl butyrate esterase. Shortly after their isolation, only the microglial cells were positive, but on continued culturing, increasing numbers of astroglial cells became positive for alpha-naphthyl butyrate esterase. By day 22, almost all of the cells were positive. Freshly isolated cells were negative for the monocyte-specific antigen Mac-1. However, after 4 days, cells with the morphology of microglia had become positive, whereas astroglia failed to exhibit this antigen with up to 22 days in culture. Thus, both astroglia and microglia have properties in common with cells of the MPS which may be useful for future studies. However, on fresh isolation only microglia were indistinguishable from monocytes for all features tested.
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PMID:Novel monocyte-like properties of microglial/astroglial cells. Constitutive secretion of lysozyme and cystatin-C. 330 35

Amyloidosis is a heterogeneous group of disorders characterized by extracellular deposition of abnormal protein fibrils which are derived from different proteins in different forms of the disease. Asymptomatic amyloid deposition in a variety of tissues is a universal accompaniment of ageing, and clinical amyloidosis is not rare. Intracerebral and cerebrovascular beta-protein amyloid deposits are a hallmark of the pathology of both sporadic and familial Alzheimer's disease, beta 2-microglobulin-derived amyloid is a common complication of long term haemodialysis, and islet amyloid polypeptide is the fibril protein in the universal islet amyloidosis of type II diabetes mellitus. New fibril proteins have lately been identified in hereditary amyloidosis, including variants of gelsolin, apolipoprotein AI, lysozyme and fibrinogen. The development of radiolabelled serum amyloid P component (SAP) scintigraphy has allowed amyloid to be diagnosed non-invasively in vivo for the first time, provided unique insight into the distribution and size of amyloid deposits, and yielded novel information on the natural history and the effects of treatment. Amyloid deposits are in a state of dynamic turnover and can regress if new fibril formation is halted. The recent elucidation of the three dimensional structure of human SAP may enable the design of specific therapeutic agents.
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PMID:Amyloidosis. 786 80

Significant advances were made this year in the understanding of serum amyloid A isotypes and in the definition of different amyloid light-chain proteins. Increasing numbers of hereditary amyloid-related transthyretin mutations have been reported (more than 30 to date). Two new hereditary amyloid proteins in several different kinships have appeared, ie, fibrinogen A alpha and lysozyme, each with a single point mutation. Both were found in patients with non-neurogenic hereditary amyloidosis with severe nephropathy. In islet amyloid polypeptide, the amyloid of adult-onset diabetes, the amino-acid sequence Ala-Ile-Leu-Ser at positions 25 to 28 appears to be critical for fibrillogenesis.
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PMID:Proteins of the systemic amyloidoses. 803 80

Amyloidoses are characterized by the deposition of non soluble proteins in tissues. Clinical aspects of hereditary amyloidoses are very diverse, and they offer many diagnosis problems to the physician. Biochemical and genetic aspects are also various. Several proteins are implicated in these hereditary diseases mainly: transthyretin, apolipoprotein A1, gelsolin, fibrinogen alpha chain and lysozyme. Studies on structural changes induced by the mutations in the transthyretin should bring new data relevant to our understanding of the amyloidogenic process. Transgenic mice with mutated transthyretin are a good model and will allow new pathogenic approach and therapeutic intervention.
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PMID:[Hereditary amyloidosis]. 805 45

Hereditary non-neuropathic systemic amyloidosis (Ostertag-type) is a rare autosomal dominant disease in which amyloid deposition in the viscera is usually fatal by the fifth decade. In some families it is caused by mutations in the apolipoprotein AI gene but in two unrelated English families under our care the amyloid deposits did not contain apoAI, despite a report that this may have been the case in one of them. Lysozyme is a ubiquitous bacteriolytic enzyme present in external secretions and in polymorphs and macrophages, but its physiological role is not always clear. Here we report that in these two families, lysozyme is the amyloid fibril protein. Affected individuals are heterozygous for point mutations in the lysozyme gene that cause substitution of highly conserved residues, namely threonine for isoleucine at position 56 in one family, and histidine for aspartic acid at residue 67 in the other. Amyloid fibrils from one individual were composed of the full-length Thr-56 variant lysozyme molecule. To our knowledge, this is the first report of naturally occurring variants of human lysozyme and of lysozyme-associated disease. As the structures of human and hen egg-white lysozyme are known to atomic resolution and their folding and structure-function relationships have been exhaustively analysed, our observations should provide a powerful model for understanding amyloidogenesis.
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PMID:Human lysozyme gene mutations cause hereditary systemic amyloidosis. 846 97

The first case of amyloidosis is reported in which spontaneous massive hepatic haemorrhage necessitated emergency liver transplantation. Liver transplantation, as a treatment for a failing liver due to amyloidosis has not been previously reported. At transplantation, the liver tissue was uncharacteristically friable, although the subsequent vascular and biliary anastomoses were uncomplicated. Histological examination of the liver showed a surprisingly modest amount of amyloid, which was shown immunohistochemically to be derived from lysozyme, and a striking absence of reticulin staining. Both the patient's father and paternal grandfather had died from spontaneous hepatic haemorrhage, and histological review of their liver tissue showed similarly modest deposition of lysozyme-derived amyloid associated with loss of reticulin staining. In each case the quantity of amyloid was far less than would be expected to interfere with the mechanical integrity of the liver. This is the only report of hepatic disintegration associated with absence of reticulin staining, and it is probable that the mechanism represents a novel secondary effect of the amyloid deposits in the livers of this family.
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PMID:'Fragile' liver and massive hepatic haemorrhage due to hereditary amyloidosis. 856 45

Metabolic processing of amyloid precursor proteins is an important factor in the genesis of practically all forms of amyloidosis. Of the three major forms of systemic amyloidosis, reactive amyloid (amyloid A protein; AA) formation shows the most consistent role of partial proteolysis of serum amyloid A (SAA) to AA proteins which form fibrils. Immunoglobulin amyloidosis is also usually associated with C-terminal degradation of the fibril precursor light chain protein. Although it is commonly thought that transthyretin amyloidosis is associated with fibril formation from the tetrameric circulating plasma transthyretin, chemical analyses of transthyretin fibril deposits show significant fragmentation of the fibril protein constituents. In addition, it has been documented that proteolytic fragments are the fibril subunit proteins in gelsolin, cystatin C. Alzheimer's beta-amyloid precursor protein and apolipoprotein AI (apoAI) amyloidoses. Notable exceptions to the role of proteolysis in amyloid fibril formation would appear to be the lysozyme and beta 2-microglobulin amyloidoses. Few studies have examined the metabolism of amyloid-forming proteins. Perhaps the best data are on apoAI, which show decreased plasma residence time for the amyloidogenic Gly26Arg apoAI (1.8 d vs. normal 4.5 d). Similarly, preliminary data show increased clearance of Val30Met transthyretin when compared with the wild-type protein (18 h vs. 26 h). Also, biosynthetically 35S-labelled SAA proteins reconstituted with HDL show increased plasma clearance of murine SAA2, the amyloid fibril subunit protein, when compared with murine SAA1. Few data are available on metabolism of amyloid immunoglobulin light chain proteins, but it has been shown that radiolabelled Bence-Jones proteins are cleared very rapidly from the circulation. A better understanding of the metabolism of precursor proteins in each of the amyloid deposition diseases will give insight into the mechanisms of fibril formation and pathogenesis of amyloidosis.
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PMID:Metabolism of amyloid proteins. 891 6

Tissue deposition of soluble proteins as amyloid fibrils underlies a range of fatal diseases. The two naturally occurring human lysozyme variants are both amyloidogenic, and are shown here to be unstable. They aggregate to form amyloid fibrils with transformation of the mainly helical native fold, observed in crystal structures, to the amyloid fibril cross-beta fold. Biophysical studies suggest that partly folded intermediates are involved in fibrillogenesis, and this may be relevant to amyloidosis generally.
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PMID:Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. 903 7

Tissue deposition of normally soluble proteins, or their fragments, as insoluble amyloid fibrils causes the usually fatal, acquired and hereditary systemic amyloidoses and is associated with the pathology of Alzheimer's disease, type 2 diabetes and the transmissible spongiform encephalopathies. Although each type of amyloidosis is characterised by a specific amyloid fibril protein, the deposits share pathognomonic histochemical properties and the structural morphology of all amyloid fibrils is very similar. We have previously demonstrated that transthyretin amyloid fibrils contain four constituent protofilaments packed in a square array. Here, we have used cross-correlation techniques to average electron microscopy images of multiple cross-sections in order to reconstruct the sub-structure of ex vivo amyloid fibrils composed of amyloid A protein, monoclonal immunoglobulin lambda light chain, Leu60Arg variant apolipoprotein AI, and Asp67His variant lysozyme, as well as synthetic fibrils derived from a ten-residue peptide corresponding to the A-strand of transthyretin. All the fibrils had an electron-lucent core but the packing arrangement comprised five or six protofilaments rather than four. The structural similarity that defines amyloid fibres thus exists principally at the level of beta-sheet folding of the polypeptides within the protofilament, while the different types vary in the supramolecular assembly of their protofilaments.
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PMID:The protofilament substructure of amyloid fibrils. 1090 51


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