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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of pituitary hormone secretion by TRH and GnRH proceeds through similar mechanisms which employ phosphoinositide hydrolysis to generate intracellular signals. Proximal events involve receptor activation of heterotrimeric (alpha beta gamma) GTP-binding (G) proteins which regulate phospholipase (PLC) activity. Since TRH and GnRH actions are not affected by cholera or pertussis toxin, a novel G protein (Gp) was suggested to mediate receptor regulation. The required Gp protein has not been identified and this was the focus of the present study. Recent molecular cloning and biochemical studies have characterized two novel, pertussis toxin-insensitive alpha-subunit proteins of the Gq subfamily (alpha q and alpha 11) which regulate the activity of the beta 1 isoenzyme of PLC. Gq and G11 represent the best candidates for the PLC-activating G proteins which mediate the actions of TRH and GnRH. To test this directly, an antibody to the common Gq/11 alpha-subunit carboxyterminal sequence was generated and shown to react with unique 42-kilodalton Gq alpha and 43-kilodalton G11 alpha proteins in membranes from TRH-responsive GH3 cells and GnRH-responsive alpha T3-1 pituitary cells. The Gq/11 alpha peptide antibody was shown to immunodeplete the Gp activity of GH3 cell membrane extracts measured by reconstitution of the guanine nucleotide regulation of PLC-beta 1. In addition, the immunoglobulin G fraction of Gq/11 alpha peptide immune serum specifically inhibited TRH- and GnRH-stimulated PLC activity measured in the membranes of GH3 and alpha T3-1 cells, respectively. The results indicate that TRH and GnRH activation of PLC requires receptor coupling to a Gp protein(s) which corresponds to Gq, G11 or both.
Mol Endocrinol 1992 Oct
PMID:Thyrotropin-releasing hormone and gonadotropin-releasing hormone receptors activate phospholipase C by coupling to the guanosine triphosphate-binding proteins Gq and G11. 133 52

The physical nature of neuronal cells, particularly in the functional and morphological segregation of synapse, soma, and dendrites, imparts special importance on the integrity of their cell membranes for the localization of function, generation of intrinsic second messengers, and plasticity required for adaptation and repair. The component phospholipids of neural membranes are important sources of bioactive mediators that participate in such diverse phenomena as memory formation and cellular damage following trauma. A common role for PAF in these processes is established through the suppressive effects of its antagonists. Furthermore, being both an extracellular and intracellular agonist of phospholipase activation, in addition to being a product of phospholipase activity, PAF assumes a centralized role in the cellular metabolism following neural stimulation. The linkage of PAF to neural immediate-early gene expression, both in vitro and in vivo, suggests that its effects are initiating to long-term formative and reparative processes. Such a common link between destructive and plastic responses provides an important view of cellular and tissue maintenance in the nervous system.
Mol Neurobiol 1992
PMID:Excitable membranes, lipid messengers, and immediate-early genes. Alteration of signal transduction in neuromodulation and neurotrauma. 133 56

Hypoxia was reported to induce a decrease in phosphatidylcholine-hydrolyzing phospholipase activity (PC-PLA) in cultured rat cardiomyocytes. This work was intended to compare the influence of the presence of either eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in the phospholipids on the PC-PLA activity in normoxic and hypoxic conditions. The enrichment of the medium with EPA or DHA resulted in cell phospholipids containing about 2% or 22% DHA, respectively. These cells were then submitted for 3.5 h to either normoxia or hypoxia and the PC-PLA activities were assayed using [1-14C] dioleoyl-PC (pH 8.4 for PC-PLA2 and 4.9 for PC-PLA1). The results show that both enzymic activities are significantly higher in DHA-rich cardiomyocytes. Hypoxia induced a significant decrease in PC-PLA2 (about 25%) which was not statistically different between the two groups of cells. The hypoxia-induced decrease in PC-PLA1 was not found significant. In conclusion, the nature of the long chain n-3 polyunsaturated fatty acids in the phospholipids appears to contribute to the regulation of PC-PLA activity but not to influence its decrease during hypoxia.
Mol Cell Biochem 1992 Oct 21
PMID:Eicosapentaenoic and docosahexaenoic acids in cultured rat ventricular myocytes and hypoxia-induced alterations of phospholipase-A activity. 148 Jan 56

Stimulation of cardiac phospholipid metabolism has diverse biological effects, ranging from subtle changes in cellular function to severe cellular damage. Accordingly, knowledge of the factors governing the activity of cardiac phospholipases is of great biological importance. A possible role of annexins, intracellular proteins that bind to membranes in a calcium dependent manner, as modulators of phospholipase activity has been proposed. In this study we investigated the cell type specific distribution of Annexin V and VIII in the heart. Recombinant Annexin V was used to examine the effect of this type of Annexin on cardiac phospholipase activity. Western blot analysis shows that annexin V is abundantly present in the heart. Using isolated myocytes and cultured cardiac endothelial and fibroblast-like cells, it is demonstrated that the localization of Annexin V is confined to non-myocytes. No positive bands matching the Mw of recombinant Annexin VIII are found in any of the cell types examined. In vitro studies demonstrate that recombinant Annexin V potently inhibits the activity of cardiac membrane-bound phospholipases, acting on their natural surrounding substrate, in a calcium dependent manner. Interestingly, annexin V also inhibits triacylglycerol hydrolysis. In conclusion, the expression of annexins is cell-type specific and suggests a cell-type specific function of these proteins in the heart. The absence of Annexin V in cardiac myocytes dismisses involvement of this annexin in cardiomyocyte phospholipid metabolism. The presence of Annexin V in cardiac endothelial and fibroblasts suggests a regulating role in the phospholipid homeostasis of non-myocyte cell types in the heart.
Mol Cell Biochem 1992 Oct 21
PMID:Annexins in cardiac tissue: cellular localization and effect on phospholipase activity. 148 Jan 59

It was shown that in LA-N-2 cells prelabeled with [3H-methyl]choline for 24 hr (Singh et al.: Mol Chem Neuropathol 14:53-66, 1991) the major intracellular and extracellular hydrophilic compound was phosphorylcholine. LA-N-2 cells were labeled with [14C-methyl]choline for 24 hr, harvested, and incubated in Hepes/BSA/saline buffer for varying periods of time. The radioactive compound present in the cytosol and released into Hepes/BSA/saline buffer medium in the presence or absence of TPA was phosphorylcholine. There was a gradual increase in the appearance of radioactivity in the medium and this corresponded to a gradual decline in the radioactivity present in the cytosolic compartment with a statistically significant P value of less than .005. Identical results were obtained with prelabeled cells subsequently incubated with TPA. There was no significant change in the amount of radioactivity associated with lipid suggesting that the phosphorylcholine may be released directly from the cytosolic compartment into the medium rather than originating through a phospholipase-C catalyzed hydrolysis of phosphatidylcholine. This possibility received support from experiments in which cells were electropermeabilized in the presence of radioactive phosphorylcholine. It was found that the introduced [14C]phosphorylcholine was released intact into the incubation medium from the cytosolic compartment. The incorporation of [14C]choline, [14C]ethanolamine, and [14C]serine by LA-N-2 cells into their corresponding phospholipids was investigated in the presence or absence of TPA. The presence of TPA increased the amount of radioactivity incorporated into the phospholipids with a corresponding decrease in the amount of radioactivity in the cytosolic compartment compared to control cultures. There were no detectable differences between TPA exposed and control cells in the distribution of radioactivity in free choline, phosphorylcholine, or CDP-choline of [14C] choline labeled cells. This indicates that the increased lipid labeling was not accompanied by enhanced labeling of the intermediates of the de novo pathway. This effect of TPA in altering the distribution of labeling of the cytosolic and lipid components was not demonstrable with cells grown in the presence of 10(-5) M retinoic acid.
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PMID:Phorbol esters modulate phospholipid metabolism in a human cholinergic cell line, LA-N-2: a possible role for the base exchange enzymes. 152 4

A single gene (plcA) was cloned from a cosmid library of Erwinia chrysanthemi EC16 DNA that encoded an extracellular phospholipase. The gene was subcloned and DNA sequence data showed the presence of a single open reading frame encoding a protein with a predicted size of 39 kDa. The coding region was G+C-rich and the protein had a predicted basic isoelectric point. The protein showed no significant homology with others in the PIR library, including other phospholipases. When overexpressed in Escherichia coli cells, the plcA gene directed production of a c. 39 kDa protein that was largely localized in the periplasm, but its N-terminal amino acid sequence was that of the native protein predicted from DNA sequence data. Unlike the wild-type bacterium, an E. chrysanthemi EC16 marker exchange mutant of the plcA gene did not secrete extracellular phospholipase activity in the medium. However, no detectable change was observed in terms of the virulence of the mutant strain on potato tubers or chrysanthemum stems.
Mol Microbiol 1992 Jan
PMID:Cloning and characterization of a phospholipase gene from Erwinia chrysanthemi EC16. 154 3

To determine whether a cloned receptor coupled to pertussis toxin (PTx)-sensitive G-proteins can induce cell proliferation and oncogenic transformation, as observed for receptors that elicit PTx-insensitive enhancement of phosphatidyl inositol (PI)-specific phospholipase-C (PLC) activity, nontransformed murine BALB/c-3T3 cells were transfected with the rat serotonin-1A (5-HT1A) receptor. The 5-HT1A receptor is coupled to PTx-sensitive G-proteins to induce a cell-specific activation of PLC. While 1 microM 5-HT induced no change in PI turnover or cytosolic free calcium levels ([Ca2+]i) in receptor-negative nontransfected 3T3 cells, 5-HT induced a 2-fold increase in inositol trisphosphate accumulation and a 2.5-fold increase in [Ca2+]i in the 3T3-ZD8 clone, which expressed 0.6 +/- 0.2 pmol/mg protein of specific 5-HT1A binding sites. The stimulatory actions of 5-HT on PI turnover and [Ca2+]i in 3T3ZD8 cells displayed the pharmacology of the 5-HT1A receptor and were abolished by pretreatment with PTx. Thus, BALB/c-3T3 fibroblast cells express the PLC-linked pathway of the 5-HT1A receptor. Overnight treatment with 5-HT (1 microM) enhanced incorporation of [3H]thymidine into DNA extracted from serum-starved 3T3ZD-8 cells, an action that was also blocked by pretreatment with pertussis toxin. Long term (1-2 weeks) exposure to 5-HT in the medium led to phenotypic transformation of the cells, including the formation of foci with 1 microM 5-HT. These actions of 5-HT were not observed in untransformed 3T3 cells. We conclude that the PTx-sensitive PLC-linked pathway of the 5-HT1A receptor expressed in nontransformed BALB/c-3T3 cells, in concert with other serum-derived factors, predisposes the cells to enhanced proliferation and transformation.
Mol Endocrinol 1992 May
PMID:Conditional transformation mediated via a pertussis toxin-sensitive receptor signalling pathway. 160 83

Many members of the genus Serratia synthesize and excrete a number of extracellular hydrolytic enzymes. One of these is the phospholipase A1 from Serratia liquefaciens, the expression of which is growth-phase-dependent. Through the use of gene fusions and primer extension analysis we show that the expression of phospholipase is subject to positive transcriptional regulation of a dual promoter system; one promoter positioned approximately 600bp upstream from the phlA gene is responsible for the induction of phospholipase expression under anaerobic conditions, and the other promoter positioned 50bp upstream from the phlA gene is subject to catabolite repression and induced during the transition from exponential to late log-phase of bacterial growth. On the basis of sequence homology and behaviour in the relevant Escherichia coli mutants, we suggest that distant promoter to be Fnr-controlled and the proximal phlA promoter to be a member of the FIbB-controlled flagellar-chemotaxis regulon.
Mol Microbiol 1992 May
PMID:Expression of extracellular phospholipase from Serratia liquefaciens is growth-phase-dependent, catabolite-repressed and regulated by anaerobiosis. 164 Aug 37

Pretreatment of Strongylocentrotus purpuratus sperm with delta 9-tetrahydrocannabinol (THC) prevents the triggering of the acrosome reaction by egg jelly. Examination of THC-treated sperm by transmission electron microscopy reveals that the membrane fusion reaction between the sperm plasma membrane and the acrosomal membrane is completely blocked. Electron-dense deposits are present in the subacrosomal fossa and in the centriolar fossa. The nuclear envelope is fragmented in close proximity to the electron-dense deposits. The electron-dense deposits are not bound by a limiting membrane, stain positively for lipid with thymol and farnesol, and disappear from THC-treated sperm that are extracted with chloroform:methanol (2:1) after glutaraldehyde fixation. The electron-dense deposits are lipid in nature and may be a hydrolytic product of the nuclear envelope. Electron-dense deposits are seen in sperm after 1-10 min treatment with 5-100 microM THC. The electron-dense deposits disappear after removal of THC from the sperm by washing, but the fragmented nuclear envelope in the subacrosomal fossa persists. Cannabidiol (CBD) and cannabinol (CBN) also inhibit the triggering of the acrosome reaction by egg jelly and produce ultrastructural changes in the sperm identical to those elicited by THC. Enhanced phospholipase activity stimulated by THC, CBD, and CBN may be the cause of the accumulation of lipid deposits in the sperm. Metabolites derived from this modification of membrane phospholipids may prevent triggering of the acrosome reaction by egg jelly and thereby inhibit fertilization.
Mol Reprod Dev 1991 May
PMID:Reduction of the fertilizing capacity of sea urchin sperm by cannabinoids derived from marihuana. II. Ultrastructural changes associated with inhibition of the acrosome reaction. 164 73

We have recently demonstrated that a 200-kDa antigen that serves as a target of antibodies acting in synergy with praziquantel is linked to the surface membrane of Schistosoma mansoni by a glycosylphosphatidylinositol (GPI) anchor. In the present study we have examined the potential role of this GPI anchor in the therapeutic action of praziquantel by monitoring the release of surface antigens from living adult schistosomes cultured in the presence or absence of praziquantel and exogenous phospholipases. Phosphatidylinositol-specific phospholipase C (PIPLC) selectively released the 200-kDa antigen from the surface of adult schistosomes, as determined by immunoprecipitation experiments; none of the other GPI-anchored proteins, including alkaline phosphatase and a 22-kDa protein, were released by this enzyme. Anti-cross-reacting determinant antiserum (anti-CRD), which recognizes an epitope on GPI-anchored proteins only after the anchor has been removed by PIPLC, specifically precipitated the 200-kDa antigen, confirming the cleavage of its anchor. When the worms were exposed to both praziquantel and PIPLC, the amount of 200-kDa cleaved from the worms was increased five-fold. The selective release of this antigen was also detected by indirect immunofluorescent labeling of praziquantel-exposed adult worms cultured in the presence of phospholipases. Taken together these observations suggest that modulation of the phospholipase-mediated release of GPI-anchored antigens by praziquantel may contribute to the therapeutic action of the drug.
Mol Biochem Parasitol 1991 May
PMID:Selective release of a glycosylphosphatidylinositol-anchored antigen from the surface of Schistosoma mansoni. 164 1


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