Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At concentrations of 0.5 microM and upward, cyclosporin A (CsA) caused dose-related inhibition of the growth of a hamster renal tubular cell line (HAK ATCC; CCL15) in vitro. Inhibition of cell growth was due to the cytotoxic properties of CsA which were associated with enhancement of activity of phospholipase A2 (PLA2) according to the increased generation of arachidonic acid and lysophosphatidylcholine (LPC). Arachidonate per se, at concentrations of up to 20 microM, did not affect the growth of HAK cells, while cyclooxygenase and 5-lipoxygenase inhibitors failed to protect the cells against the antiproliferative effects of CsA. However, LPC caused dose-related inhibition of the growth of HAK cells. Moreover, coincubation with lysophospholipase or alpha-tocopherol (AT, vitamin E), a PLA2 inhibitory and lysophospholipid-complexing agent, protected the HAK cells against both CsA and LPC. The Na+, K(+)-ATPase activity of HAK cells was also inhibited by CsA, with the enzyme being protected by inclusion of AT or lysophospholipase. Increased activity of PLA2 and inhibition of Na+, K(+)-ATPase preceded cytotoxicity and cytolysis. Excessive production of lysophospholipids and consequent inhibition of Na+, K(+)-ATPase in renal tubular cells is a possible mechanism of CsA-induced nephrotoxicity. The protective effects of AT suggest that this agent may be clinically useful in preventing the renal side effects of CsA.
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PMID:Alpha-tocopherol prevents cyclosporin A-mediated activation of phospholipase A2 and inhibition of Na+, K(+)-adenosine triphosphatase activity in cultured hamster renal tubular cells. 817 26

The relationship between the phospholipase-stimulating and immunosuppressive properties of cyclosporin A (CsA) has been investigated in vitro. At concentrations of 0.025 microM and upwards, CsA caused dose-related inhibition of both mitogen- and alloantigen-stimulated uptake of tritiated thymidine by human mononuclear leukocytes (MNL), which was associated with a time- and dose-related enhancement of the generation of lysophosphatidylcholine (LPC), arachidonic acid, and prostaglandin E2 from mitogen-stimulated cells. Arachidonate alone, at concentrations of up to 20 microM, did not affect lymphocyte activation, whereas cyclooxygenase and 5'-lipoxygenase inhibitors failed to protect the cells against the antiproliferative effects of CsA. However, LPC caused dose-related inhibition of MNL proliferation. Moreover, coincubation of MNL with alpha-tocopherol, a lysophospholipid-complexing agent, or with lysophospholipase protected the cells against CsA, as well as against LPC. The Na+,K(+)-ATPase activity of mitogen-activated lymphocytes was also inhibited by CsA, whereas inclusion of alpha-tocopherol or lysophospholipase protected this enzyme. Excessive production of lysophospholipids and consequent inhibition of Na+,K(+)-ATPase during CsA treatment of mitogen- or antigen-activated lymphocytes is a possible biochemical mechanism of the immunosuppressive activity of this agent.
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PMID:Lysophospholipid-mediated inhibition of Na+,K(+)-adenosine triphosphatase is a possible mechanism of immunosuppressive activity of cyclosporin A. 839 20

Previously, we had demonstrated that a Legionella pneumophila prepilin peptidase (pilD) mutant does not produce type IV pili and shows reduced secretion of enzymatic activities. Moreover, it displays a distinct colony morphology and a dramatic reduction in intracellular growth within amoebae and macrophages, two phenotypes that are not exhibited by a pilin (pilE(L)) mutant. To determine whether these pilD-dependent defects were linked to type II secretion, we have constructed two new mutants of L. pneumophila strain 130b. Mutations were introduced into either lspDE, which encodes the type II outer membrane secretin and ATPase, or lspFGHIJK, which encodes the pseudopilins. Unlike the wild-type and pilE(L) strains, both lspDE and lspG mutants showed reduced secretion of six pilD-dependent enzymatic activities; i.e., protease, acid phosphatase, p-nitrophenol phosphorylcholine hydrolase, lipase, phospholipase A, and lysophospholipase A. However, they exhibited a colony morphology different from that of the pilD mutant, suggesting that their surfaces are distinct. The pilD, lspDE, and lspG mutants were similarly and greatly impaired for growth within Hartmannella vermiformis, indicating that the intracellular defect of the peptidase mutant in amoebae is explained by the loss of type II secretion. When assessed for infection of U937 macrophages, both lsp mutants exhibited a 10-fold reduction in intracellular multiplication and a diminished cytopathic effect. Interestingly, the pilD mutant was clearly 100-fold more defective than the type II secretion mutants in U937 cells. These results suggest the existence of a novel pilD-dependent mechanism for promoting L. pneumophila intracellular infection of human cells.
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PMID:Type II protein secretion is a subset of the PilD-dependent processes that facilitate intracellular infection by Legionella pneumophila. 1125 62

The effects of the anti-proliferative, phospholipase A(2) (PLA(2))-activating riminophenazine agents, clofazimine and B669, on the Na+, K+-adenosine triphosphatase activity of the FaDu human pharynx squamous carcinoma cell line have been investigated in vitro. At concentrations of 1.25-10 mu g/ml both agents caused dose-related enhancement of PLA(2), as measured by increased release of lysophosphatidylcholine (LPC), and inhibition of Na+, K+-ATPase in intact cells and isolated membrane preparations. The inhibitory effects of both riminophenazines on the Na+, K+-ATPase activity of FaDu cells were mimicked by reagent LPC and prevented by treatment of the cells with the lysophospholipid-neutralizing agents alpha-tocopherol and lysophospholipase. Riminophenazine-mediated inhibition of Na+, K+-ATPase activity was also observed with the HeLa (human cervix epitheloid carcinoma) and T24 (human transitional cell bladder carcinoma) cell lines. The anti-proliferative activity of clofazimine and B669 is therefore probably achieved by lysophospholipid-mediated inactivation of Na+, K+-ATPase.
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PMID:The antiproliferative riminophenazine agents clofazimine and b669 promote lysophospholipid-mediated inhibition of na+, k+-adenosine triphosphatase-activity in cancer cell-lines in-vitro. 2156 28