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)

Membrane attack complex (MAC) inhibitory factor (MACIF) is a 20-kD membrane protein that inhibits MAC formation on homologous cells. Until recently, a functional role of MACIF had been demonstrated in erythrocytes. Therefore, we have focused on the fact that glomerular epithelial cells (GECs) are the primary target of MAC-mediated damage in rat Heymann's nephritis model of human membranous nephropathy. Using immunocytochemistry and western blotting we have shown that MACIF is expressed in cultured human GECs. Phosphatidyl-inositol (PI)-phospholipase C (PLC) reduced MACIF expression in these cells, suggesting that MACIF is a PI-linked membrane protein in GECs. In addition, we elucidated that MACIF protects GECs against complement-mediated lysis. These findings suggest that MACIF expressed on GECs plays an important role in the protection of GECs against complement mediated-cellular damage in vivo.
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PMID:[Significance of membrane attack complex inhibitory factor expression in cultured human glomerular epithelial cells]. 813 53

Glomerular infiltration of blood-derived mononuclear cells contributes to the glomerular injury in the autologous phase of nephrotoxic nephritis (NTN). LysoPAF has recently been shown to be chemotactic for human monocytes, thus its accumulation might account for monocyte recruitment. We investigated [3H]lysoPAF metabolism in isolated glomeruli from normal and NTN rabbits studied both in the heterologous and in the autologous phases of the disease. [3H]lysoPAF was converted to [3H]1-O-alkyl-glycerol and [3H]1-O-alkyl-2-acyl-GPC by phospholipase C and acyltransferase, respectively, both in normal and NTN glomeruli. Glomerular metabolism of [3H]lysoPAF was normal during the heterologous phase of NTN. By contrast, in isolated glomeruli from NTN rabbits studied in the autologous phase of the disease, a significantly lower [3H]lysoPAF degradation occurred with respect to normal ones. This defective degradation resulted in a significantly reduced formation of [3H]1-O-alkyl-glycerol. The apparent Km for enzymatic conversion of [3H]lysoPAF to [3H]1-O-alkyl-glycerol, determined at 15 minutes as a function of [3H]lysoPAF concentration, was doubled in glomeruli from rabbits studied in the autologous phase of NTN as compared to normal ones, while Vmax values were similar in the two groups. These results show a defective glomerular lysoPAF degradation in the autologous phase of NTN, likely due to a decreased affinity of phospholipase C to lysoPAF. Altered lysoPAF metabolism results in glomerular accumulation of lysoPAF in the autologous phase of NTN, as shown by significantly higher levels of lysoPAF measured in nephritic glomeruli as compared to normal ones.
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PMID:Defective glomerular [3H]lysoPAF metabolism in the autologous phase of rabbit nephrotoxic nephritis. 825 52

Thy-1 glycoprotein is expressed in rat glomerular mesangial cells, and anti-Thy-1 nephritis induced by anti-Thy-1 antibodies is a model of human renal diseases. In this study, we examined Thy-1-mediated biological reactions in cultured rat glomerular mesangial cells utilizing two anti-Thy-1 monoclonal antibodies (mAbs), 1-22-3 and OX-7. Incubation of the cells with these mAbs resulted in increased inositol trisphosphate (IP3) levels. The rise in IP3 produced by mAb 1-22-3 was greater than that produced by mAb OX-7 at the same dose. Incubation of mesangial cells with these mAbs resulted in an increase in the intracellular free calcium concentration ([Ca2+]i). mAb 1-22-3 induced a sustained increase in [Ca2+]i, while that induced by mAb OX-7 lasted 1-2 min, then decreased to the basal level. An transient increase in [Ca2+]i was also observed in Ca(2+)-free medium, indicating that these [Ca2+]i increases are due to release of Ca2+ from internal stores by IP3 without calcium flux across cell membrane. When cells were pretreated with protein tyrosine kinase (PTK) inhibitors (herbimycin A or genistein), Thy-1-mediated increases in [Ca2+]i were inhibited. These data suggest that Thy-1 induces the production of IP3 (including inositol 1,4,5-triphosphate, an intracellular Ca(2+)-releasing factor) and that PTKs may contribute to the Thy-1-mediated elevation of [Ca2+]i which presumably results from phospholipase C activation following Thy-1-mediated signaling in rat mesangial cells.
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PMID:Thy-1-mediated phosphatidylinositol turnover in cultured rat glomerular mesangial cell. 881 25

Leukotriene D4 (LTD4) is one of the slow-reacting substances of anaphylaxis and is reported to have a diverse response including the mediation of glomerular nephritis. However, little is known about the functions of LTD4 and its mechanisms of action in primary cultured rabbit renal proximal tubular cells (PTCs). The purpose of this study is to investigate the effect of LTD4 on Na+ uptake and its related signal transduction pathways in PTCs. LTD4 (>10(-9) M) significantly inhibited the Na+ uptake after 15 min (in nmol/mg protein: controls 431.7+/-11.4 vs. LTD4 (10(-9) M) 355.0+/-23.6; p<0. 05); and its effect was blocked by MK-571 (10(-6) M), a leukotriene receptor antagonist, in PTCs. Preincubation with cilastatin, a renal dipeptidase inhibitor, and polyclonal antibody against renal dipeptidase potentiated the inhibitory effect of LTD4 on Na+ uptake. SQ 22536 (10(-6) M), an adenylate cyclase inhibitor, and the myristoylated protein kinase A inhibitor amide 14-22 (PKI; 10(-5) M) blocked the effect of LTD4 on Na+ uptake (in nmol/mg protein: LTD4 349.9+/-18.5 vs. SQ 22536+LTD4 476.5+/-22.0 and PKI+LTD4 440.3+/-19. 3; p<0.05), and LTD4 induced an increase in cyclic adenosine monophosphate (cAMP), suggesting the involvement of cAMP in the inhibition of Na+ uptake. In addition, U 73122 (10(-6) M) and neomycin (10(-4) M), phospholipase C (PLC) inhibitors, W-7 (10(-4) M), a calmodulin antagonist, and bisindolylmaleimide I, a protein kinase C (PKC) inhibitor, blocked the LTD4-induced inhibition of Na+ uptake, strongly suggesting involvement of the PLC-PKC signal pathways in the effect of LTD4. LTD4 significantly increased [Ca2]i by 49+/-7% as compared with baseline. TMB-8 (10(-5) M) and BAPTA/AM (10(-5) M), intracellular calcium mobilization blockers, completely blocked the LTD4-induced inhibition of Na+ uptake (in nmol/mg protein: LTD4 347.6+/-19.0 vs. TMB-8+LTD4 436.4+/-22.3 and BAPTA/AM+LTD4 419.9+/-14.3; p<0.05); however, EGTA (1 mM), a calcium chelator, partially blocked the LTD4-induced inhibition of Na+ uptake. In conclusion, LTD4-induced inhibition of Na+ uptake may be involved in both cAMP and PLC-PKC signal pathways in PTCs. In addition, Ca2+, which comes from the intracellular Ca2+ mobilization, is primarily responsible for the LTD4-induced inhibition of Na+ uptake.
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PMID:Leukotriene D4 inhibits Na+ uptake through cAMP and PLC pathways in primary cultured renal proximal tubular cells. 1039 8