Characterization of phospholipase C-mediated polyphosphoinositide hydrolysis in rat heart ventricles

Schwertz, Dorie W.; Halverson, Jennifer B.

doi:10.1016/0003-9861(89)90094-5

Cited by 16 publications

(5 citation statements)

References 33 publications

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“…Indeed, the activation of PKC-δ is dependent on diacylglycerol (DAG), a second messenger signaling lipid that also stimulates Ca 2+ i -release9. Importantly, Gd 3+ stimulates the activity of the phospholipase C (PLC) enzyme required for the production of DAG33, suggesting that Gd 3+ targets both Ca 2+ i and DAG production. Also, Gd 3+ induced Shh gene expression more potently than thapsigargin or carbachol, which could be mediated by Ca 2+ i -release and DAG production acting synergistically to stimulate Shh expression.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Calcium Release and Protein Kinase C Activation Stimulate Sonic Hedgehog Gene Expression During Gastric Acid Secretion

et al. 2010

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Introduction Hypochlorhydria during Helicobacter pylori infection inhibits gastric Shh expression. We investigated whether acid-secretory mechanisms regulate Shh gene expression through Ca2+i-dependent protein kinase C (PKC) or cAMP-dependent protein kinase A (PKA)-activation. Method We blocked Hedgehog signaling by transgenically overexpressing a secreted form of the Hedgehog interacting protein-1 (sHip-1), a natural inhibitor of hedgehog ligands, which induced hypochlorhydria. Gadolinium, EGTA+BAPTA, PKC-overexpressing adenoviruses, and PKC-inhibitors were used to modulate Ca2+i-release, PKC-activity and Shh gene expression in primary gastric cell, organ, and AGS cell line cultures. PKA hyperactivity was induced in the H+/K+-β-cholera-toxin overexpressing mice (Ctox). Results Mice that expressed sHip-1 had lower levels of gastric acid (hypochlorhydria), reduced production of somatostatin, and increased gastrin gene expression. Hypochlorhydria in these mice repressed Shh gene expression, similar to the levels obtained with omeprazole treatment of wild-type mice. However, Shh expression was also repressed in the hyperchlorhydric Ctox model with elevated cAMP, suggesting that the regulation of Shh was not solely acid-dependent, but pertained to specific acid-stimulatory signaling pathways. Based on previous reports that Ca2+i-release also stimulates acid secretion in parietal cells, we showed that gadolinium-, thapsigargin- and carbachol-mediated release of Ca2+i induced Shh expression. Ca2+-chelation with BAPTA+EGTA reduced Shh expression. Overexpression of PKC-α, -β and -δ (but not PKC-ε) induced Shh gene expression. In addition, phorbol esters induced a Shh-regulated reporter gene. Conclusion Secretagogues that stimulate gastric acid secretion induce Shh gene expression through increased Ca2+i-release and PKC activation. Shh might be the ligand transducing changes in gastric acidity to the regulation of G-cell secretion of gastrin.

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Section: Discussionmentioning

confidence: 99%

Intracellular Calcium Release and Protein Kinase C Activation Stimulate Sonic Hedgehog Gene Expression During Gastric Acid Secretion

et al. 2010

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“…In macrophages, a localised increase in PtdIns(4,5)P 2 in the nascent phagosome occurs at the onset of phagocytosis (Botelho et al, ) resulting in a robust increase in actin polymerisation required for the extension of pseudopods. This upsurge in PtdIns(4,5)P 2 concentration results from either synthesis by PIPKI enzyme (Ishihara et al, ) or inhibition of its hydrolysis (Schwertz & Halverson, ). Nothing is known about the role of PtdIns(4,5)P 2 metabolism and the enzymes involved in its generation during phagocytosis in E. histolytica except a few reports describing the effect of wortmannin, an inhibitor of PtdIns(3,4,5)P 3 generating enzyme on inhibition of uptake in E. histolytica (Marion, Laurent, & Guillen, ).…”

Section: Introductionmentioning

confidence: 99%

Novel regulatory roles of PtdIns(4,5)P₂generating enzyme EhPIPKI in actin dynamics and phagocytosis ofEntamoeba histolytica

Sharma

Agarwal

Bharadwaj

et al. 2019

Cellular Microbiology

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Motility and phagocytosis are the two important processes that are intricately linked to survival and virulence potential of the protist parasite Entamoeba histolytica. These processes primarily rely on actin-dependent pathways, and regulation of these pathways is critical for understanding the pathology of E. histolytica. Generally, phosphoinositides dynamics have not been explored in amoebic actin dynamics and particularly during phagocytosis in E. histolytica. We have explored the roles of PtdIns(4,5)P 2 as well as the enzyme that produces this metabolite, EhPIPKI during phagocytosis. Immunofluorescence and live cell images showed enrichment of EhPIPKI in different stages of phagocytosis from initiation till the cups progressed towards closure. However, the enzyme was absent after phagosomes are pinched off from the membrane. Overexpression of a dominant negative mutant revealed a reduction in the formation of phagocytic cups and inhibition in the rate of engulfment of erythrocytes. Moreover, EhPIPKI binds directly to F and G-actin unlike PIPKs from other organisms. PtdIns(4,5)P 2 , the product of the enzyme, also followed a similar distribution pattern during phagocytosis as determined by a GFP-tagged PH-domain from PLCδ, which specifically binds PtdIns(4,5)P 2 in trophozoites. In summary, EhPIPKI regulates initiation of phagocytosis by regulating actin dynamics.

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“…Components of the phosphoinositide turnover second-messenger system have been identified in heart, including PIC (Low & Weglicki, 1983;McDonald & Mamrack, 1988;Schwertz et al, 1987Schwertz et al, , 1989). In heart, PIC is activated by endothelin, muscarinic, ar-adrenergic, or purinergic agonists, as well as by electrical stimulation (Ambar et al, 1989;Brown & Brown, 1983; Haggblad & Heilbronn, 1988; Poggioli et al, 1986).…”

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confidence: 99%

“…Increased intracellular calcium stimulates PIC in some cell types including cultured cardiomyocytes (Godfrey & Putney, 1984;Martin et al, 1986;McDonough et al, 1988;Monaco, 1987a), but not in other cell types (Fisher et al, 1985;McMillian et al, 1988; Murayama & Ui, 1987; Nakamura & Ui, 1985;Renard et al, 1987;di Virgilio et al, 1985), indicating that PIC activity is not under identical control in all tissues. Heart PIC activity measured in vitro is Ca2+ dependent, demonstrated by a sensitivity to the chelator EGTA (McDonald & Mamrack, 1988;Schwertz et al, 1987Schwertz et al, , 1989. Purified PIC isozymes are activated by Ca2+ concentrations from 0 to 1 /uM (Bennett & Crooke, 1987;Hofmann & Majerus, 1982;Homma et al, 1988;Ryu et al, 1987).…”

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confidence: 99%

Purification and characterization of bovine heart phosphoinositide-specific phospholipase C: kinetic analysis of the calcium requirement and lanthanum(3+) inhibition

McDonald¹,

Mamrack²

1989

Biochemistry

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Bovine heart contains multiple phosphoinositide-specific phospholipase C (PIC) activities separable by ion-exchange chromatography. One PIC activity was purified to apparent homogeneity and migrated as a single band of Mr 85,000 on SDS-PAGE. The purified PIC was characterized with sonicated suspensions of either pure phosphatidylinositol 4,5-bisphosphate (PIP2) or phosphatidylinositol (PI) as substrates. At pH 7, apparent Vmax and Km values were higher for PIP2 than for PI, but the value of Vmax/Km was similar for the two substrates. PIC required Ca2+ for the hydrolysis of either PI or PIP2, and increasing free Ca2+ concentrations from 20 to 300 nM saturated PIC activity. The requirement of Ca2+ for PIC activity and the sensitivity of PIC to Ca2+ concentrations in the physiological range suggested the ion may be a cofactor. The PIC reaction mechanism was determined by two-substrate kinetic analysis; the data fit a model in which PIC contained single sites for Ca2+ and phosphoinositide, and utilized a rapid-equilibrium, random-order ternary mechanism for phosphoinositide hydrolysis. The KCa value for either PI or PIP2 hydrolysis was approximately 30 nM, suggesting resting intracellular free Ca2+ concentrations are sufficient to saturate the Ca2+ site of PIC. La3+ was used as a calcium analogue to modulate PIC activity. Low concentrations of LaCl3 (0.01-0.3 microM) inhibited PIC activity competitively with respect to calcium, consistent with a Ca2+ binding site on the enzyme.

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Characterization of phospholipase C-mediated polyphosphoinositide hydrolysis in rat heart ventricles

Cited by 16 publications

References 33 publications

Intracellular Calcium Release and Protein Kinase C Activation Stimulate Sonic Hedgehog Gene Expression During Gastric Acid Secretion

Intracellular Calcium Release and Protein Kinase C Activation Stimulate Sonic Hedgehog Gene Expression During Gastric Acid Secretion

Novel regulatory roles of PtdIns(4,5)P₂generating enzyme EhPIPKI in actin dynamics and phagocytosis ofEntamoeba histolytica

Purification and characterization of bovine heart phosphoinositide-specific phospholipase C: kinetic analysis of the calcium requirement and lanthanum(3+) inhibition

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Characterization of phospholipase C-mediated polyphosphoinositide hydrolysis in rat heart ventricles

Cited by 16 publications

References 33 publications

Intracellular Calcium Release and Protein Kinase C Activation Stimulate Sonic Hedgehog Gene Expression During Gastric Acid Secretion

Intracellular Calcium Release and Protein Kinase C Activation Stimulate Sonic Hedgehog Gene Expression During Gastric Acid Secretion

Novel regulatory roles of PtdIns(4,5)P2generating enzyme EhPIPKI in actin dynamics and phagocytosis ofEntamoeba histolytica

Purification and characterization of bovine heart phosphoinositide-specific phospholipase C: kinetic analysis of the calcium requirement and lanthanum(3+) inhibition

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Novel regulatory roles of PtdIns(4,5)P₂generating enzyme EhPIPKI in actin dynamics and phagocytosis ofEntamoeba histolytica