Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblasts cultured from patients with various forms of neuronal ceroid-lipofuscinosis (NCL; Batten disease) showed variably decreasing cathepsin B activity with increasing passage number and months in culture in the presence of fetal calf serum. Cathepsin H activity and that of a wide range of lysosomal hydrolases was unaffected by these conditions. Cathepsin B activity was assayed either colorimetrically (N alpha-benzoyl-DL-Arg-beta-naphthylamide; BANA), fluorimetrically (Z-Arg-Arg-methylcoumarin), or autoradiographically, following NaDodSO4-12.5% polyacrylamide gel electrophoresis ([125]Tyr-Ala-Lys-Arg-CH2Cl) and was found to be lysosomal in localization. Fractionation of disrupted fibroblasts on a Percoll gradient showed evidence of abnormally buoyant lysosomes in some NCL patients, and these tended to be low in cathepsin B but rich in other lysosomal hydrolases. Our data do not support a primary defect in cathepsin B as the basic defect in NCL. However, a possible explanation for various studies implicating a protease defect in NCL is that cathepsin B was highly sensitive to inactivation by peroxides and aldehydes. Thus hydrogen peroxide (0.3 mM) or 4-hydroxynonenal (1 nM) inactivated cathepsin B without inhibiting cathepsin H or lysosomal hydrolases such as alpha-L-fucosidase. Since peroxides and 4-hydroxynonenal have been shown to accumulate in NCL tissue (despite apparently normal peroxidase activity), we tested the possibility of a defect in the removal of peroxidized lipids from phospholipids as the primary defect in NCL. The nociceptive peptide bradykinin (BK) normally initiates a cascade involving receptor-mediated phospholipase C activation and release of arachidonate and prostanoids from cultured skin fibroblasts. Release of [3H]arachidonate by BK was deficient in NCL fibroblasts, suggesting that the primary defect in NCL could involve the deficiency of a specific phospholipase A2 activity.
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PMID:Abnormal cathepsin B activity in Batten disease. 314 18

The platelets of a young man with the grey platelet syndrome were severely depleted of all seven alpha-granule proteins assayed as well as partially deficient in alpha-mannosidase and alpha-fucosidase; four other lysosomal enzymes were present in normal concentrations. Total platelet 5-hydroxytryptamine (5HT) and adenine nucleotides were normal, and 14C-5HT uptake reached normal levels only slightly more slowly than a control. Aggregation and dense body secretion occurred normally in response to ADP, adrenaline, collagen, PAF-acether, sodium arachidonate, A23187, Ionomycin, TPA and U44069, but were very delayed in response to thrombin. The increase in cytosolic free calcium in response to thrombin was very slow and much reduced in amplitude, whether in the presence or absence of extracellular Ca2+. These defects in response to thrombin were not corrected by the separate addition of purified alpha-granule proteins or by a whole releasate from normal platelets. It is suggested that these platelets, in addition to their alpha-granule deficiency, may have a specific defect of thrombin receptor-mediated activation of phospholipase C.
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PMID:Grey platelet syndrome: studies on platelet alpha-granules, lysosomes and defective response to thrombin. 358 Mar

Strong phospholipase A (PLA) and phospholipase C (PLC) activities as potential virulence factors are the outstanding characteristics of eight strains of small oral spirochaetes isolated from deep periodontal lesions. By qualitative dot-blot DNA-DNA hybridization and 16S rDNA sequence comparison, these spirochaetes form a distinct phylogenetic group, with Treponema maltophilum as its closest cultivable relative. Growth of these treponemes, cells of which contain two endoflagella, one at each pole, was autoinhibited by the PLA-mediated production of lysolecithin unless medium OMIZ-Pat was prepared without lecithin. N-Acetylglucosamine was essential and D-ribose was stimulatory for growth. All isolates were growth-inhibited when 1% foetal calf serum was added to the medium. Growth on agar plates supplemented with human erythrocytes produced haemolysis. In addition to PLA and PLC, the new isolates displayed strong activities of alkaline and acid phosphatases, beta-galactosidase, beta-glucuronidase, N-acetyl-beta-glucosaminidase and sialidase, intermediate activities of C4- and C8-esterases, naphthol phosphohydrolase and alpha-fucosidase and a distinctive 30 kDa antigen detectable on Western blots. This phenotypically and genotypically homogeneous group is proposed as a novel species, Treponema lecithinolyticum sp. nov., with isolate OMZ 684T designated as the type strain. A molecular epidemiological analysis using a T. lecithinolyticum-specific probe showed this organism to be associated with affected sites when compared with unaffected sites of periodontitis patients. This association was more pronounced in patients with rapidly progressive periodontitis than in those with adult periodontitis.
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PMID:Treponema lecithinolyticum sp. nov., a small saccharolytic spirochaete with phospholipase A and C activities associated with periodontal diseases. 1055 10

The membrane anchoring of the following glycohydrolases of human erythrocyte plasma membranes was investigated: alpha- and beta-D-glucosidase, alpha- and beta-D-galactosidase, beta-D-glucuronidase, N-acetyl-beta-D-glucosaminidase, alpha-D-mannosidase, and alpha-L-fucosidase. Optimized fluorimetric methods for the assay of these enzymes were set up. Treatment of the ghost preparation with 1.0 mol/l (optimal concentration) NaCl caused release ranging from 4.2% of alpha-D-glucosidase to 70% of beta-D-galactosidase; treatment with 0.4% (optimal concentration) Triton X-100 liberated 5.1% of beta-D-galactosidase to 89% of alpha-D-glucosidase; treatment with 1.75% (optimal concentration) octylglucoside yielded solubilization from 6.3% of beta-D-galactosidase to 85% of alpha-D-glucosidase. Treatment with phosphoinositide-specific phospholipase C caused no liberation of any of the studied glycohydrolases. These results are consistent with the notion that the above glycohydrolases are differently anchored or associated with the erythrocyte plasma membrane, and provide the methodological basis for inspecting the occurrence of these enzymes in different membrane microdomains.
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PMID:Membrane anchoring and surface distribution of glycohydrolases of human erythrocyte membranes. 1080 66