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)

With respect to normal tissues, 31P NMR spectra of tumors usually exhibit elevated phosphomonoester (PME) and phosphodiester (PDE) signals, arising from phospholipid metabolites such as phosphocholine (PCho) and glycerophosphocholine (GroPCho) (and/or ethanolamine analogues). PME and PDE resonances may undergo significant alterations during tumor growth, at early stages of tumor response to treatment or following cell differentiation and maturation. The enzymatic mechanisms which regulate these alterations are scarcely understood. Recent studies on agonist-induced phosphatidylcholine (PC) hydrolysis by PC-specific phospholipase C (PC-plc) in cells stimulated by hormones or growth factors suggest the hypothesis that repeated transient activations of this enzyme may also contribute to the elevation of PCho levels in tumor NMR spectra. This paper reports the first direct evidence on neutral active PC-plc activity in a tumour cell system, Friend leukemia cells, either in the undifferentiated (FLC) or differentiated state (dFLC). Cell homogenates were incubated in the presence of mixed diheptanoylphosphatidylcholine/sphingomyelin unilamellar vesicles (SLUV), which were previously shown to represent a good substrate for bacterial plc. 31P NMR analyses allowed the simultaneous detection and quantification of phosphorylated metabolites produced in tumor cell homogenates by PC-plc activity, as well by enzymes active in the PC deacylation pathway. With respect to FLC, dFLC homogenates exhibited higher PC-plc activity and lower accumulation of a deacylation product, GroPCho, in agreement with the elevation in the [PCho]/[GroPCho] ratio, already reported in 31P NMR spectra of intact differentiated cells. The direct detection of PC-plc in this cell system opens novel biochemical interpretations on a series of oncological observations, such as a) transient increases in the levels of PCho and PC-derived diacylglycerols reported in immature or in transformed cells in response to agonist-receptor interactions and b) accumulation of mobile lipids in tumor cell membranes and tissues.
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PMID:Detection of neutral active phosphatidylcholine-specific phospholipase C in Friend leukemia cells before and after erythroid differentiation. 829 51

The cardiotonic steroid marinobufagenin (MBG) has been implicated in the pathogenesis of experimental uremic cardiomyopathy, which is characterized by progressive cardiac fibrosis. We examined whether the transcription factor Friend leukemia integration-1 (Fli-1) might be involved in this process. Fli-1-knockdown mice demonstrated greater cardiac collagen-1 expression and fibrosis compared with wild-type mice; both developed increased cardiac collagen expression and fibrosis after 5/6 nephrectomy. There was a strong inverse relationship between the expressions of Fli-1 and procollagen in primary culture of rat cardiac and human dermal fibroblasts as well as a cell line derived from renal fibroblasts and MBG-induced decreases in nuclear Fli-1 as well as increases in procollagen-1 expression in these cells. Transfection of a Fli-1 expression vector prevented increased procollagen-1 expression from MBG. MBG exposure induced a rapid translocation of the delta-isoform of protein kinase C (PKCdelta) to the nucleus. This translocation was prevented by pharmacological inhibition of phospholipase C, and MBG-induced increases in procollagen-1 expression were prevented with a PKCdelta- but not a PKCalpha-specific inhibitor. Finally, immunoprecipitation studies strongly suggest that MBG induced phosphorylation of Fli-1. We feel these data support a causal relationship with MBG-induced translocation of PKCdelta, which results in phosphorylation of as well as decreases in nuclear Fli-1 expression, which, in turn, leads to increases in collagen production. Should these findings be confirmed, we speculate that this pathway may represent a therapeutic target for uremic cardiomyopathy as well as other conditions associated with excessive fibrosis.
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PMID:Marinobufagenin induces increases in procollagen expression in a process involving protein kinase C and Fli-1: implications for uremic cardiomyopathy. 1926 38