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Regulation of the Arachidonic Acid Cascade and PAF Metabolism in Reproductive Tissues
Published in Murray D. Mitchell, Eicosanoids in Reproduction, 2020
John M. Johnston, Noriei Maki, Marlane J. Angle, Dennis R. Hoffman
Glycerophospholipid degradation in mammalian tissue is primarily catalyzed by the action of phospholipases, as illustrated in Figure 2. With the exception of phosphatidylinositol, most glycerophospholipids are degraded via phospholipase A enzymes. The phosphatidylinositol pathway employs phospholipase C; the products of this reaction are inositol phosphate(s) and diacylglycerol. The role of the inositol polyphosphates and diacylglycerol as second messengers and the relationship of Ca2+ to signal transduction and protein kinase C activity have recently been reviewed.31,32 More recently, a role for phospholipase D, which has been purified from mammalian tissues,33 has been implicated in the generation of phosphatidic acid, which may subsequently function as a second messenger.34
Methods to Study Endothelium-Dependent Responses
Published in Thomas F. Lüscher, Paul M. Vanhoutte, The Endothelium: Modulator of Cardiovascular Function, 2020
Thomas F. Lüscher, Paul M. Vanhoutte
The enzyme phospholipase C catalyzes the breakdown of phosphatidylinositol 4,5-biphosphate, phosphatidylinositol-4-phosphate, and phosphatidylinositol and leads to the formation of inositol 1,4,5-trisphosphate and diacylglycerol.428,484,790,998,1006–1008,1019 The formation of the second messengers inositol trisphosphate and diacylglycerol can be measured by incubating the cells either with labeled phospholipids (3H-myoinositol or 14C-glycerol) or with labeled phosphorus (32Pi).12,428,1019,1020
Phosphatidylinositol and inositolphosphatide metabolism in hypertrophied rat heart
Published in H. Saito, Y. Yamori, M. Minami, S.H. Parvez, New Advances in SHR Research –, 2020
Hideaki Kawaguchi, Akira Kitabatake
Phospholipase C activity. The preliminary study determined that the optimal pH for phospholipase C (PI-PLC) was 7.0, and the substrate specificity of phospholipase C in hearts was previously determined (Kawaguchi and Yasuda, 1988a). Each subcellular fraction was incubated with [14C]arachidonic acid- labeled phospholipids (50,000 cpm/20 nmol) in 0.1 M Tris-HCl, pH 7.0, 5 mM CaCl2 for 2 min at 37°C. The released diacylglyceride (DAG) and free arachi-donic acid were extracted by the method of Folch et al. (1957). The chloroform phase was pooled and evaporated under vacuum. The residues were applied to thin-layer chromatography, which was developed in diethylether/acetic acid (96:4,vol/vol) and then again in a solvent system containing petroleum ether/ diethylether/acetic acid vol/vol/ vol) (Kawaguchi and Yasuda, 1986a). The respective spots of monoglyceride, diglyceride, triglyceride, and arachidonic acid were scraped, counted with a scintillation spectrometer, and analyzed according to previous studies (Kawaguchi and Yasuda, 1986b).
Loss of mGluR1-LTD following cocaine exposure accumulates Ca2+-permeable AMPA receptors and facilitates synaptic potentiation in the prefrontal cortex
Published in Journal of Neurogenetics, 2021
We further investigated the downstream signaling mechanism underlying this mPFC mGluR1-LTD. Bath application of rapamycin (40 nM), a potent inhibitor of mTOR that mediates several forms of mGluR1/5-LTD in a protein synthesis-dependent manner (Collingridge, Peineau, Howland, & Wang, 2010; Hou & Klann, 2004; Klann & Dever, 2004; Mameli et al., 2007), fully blocked the DHPG-LTD (Figure 1(D,F), −7.18 ± 15.29%). Interestingly, co-application of U73122 (10 µM), a specific inhibitor of phospholipase C (PLC) that mediates much of the canonical mGluR1/5 signaling and mGluR1/5-LTD in several brain regions (Collingridge et al., 2010), failed to inhibit this DHPG-LTD (Figure 1(E,F), −43.27 ± 9.68%). Thus, this signaling pathway is unlikely to be involved in this mPFC mGluR1-LTD uncovered here. Finally, we examined whether this mGluR1-LTD is expressed pre- or postsynaptically. Using a paired-pulse stimulation protocol that assesses changes in presynaptic release mechanism (Zucker & Regehr, 2002), we found that the paired-pulse ratio (PPR) was similar before and after DHPG application (Figure 1(G,H), before: 1.79 ± 0.32 vs. after 2.06 ± 0.27), indicating unaltered presynaptic transmitter release following DHPG application. Taken together, our results uncovered a previously unreported mGluR1-dependent, mTOR-mediated, and postsynaptically expressed LTD in deep-layer neurons of the mouse mPFC.
Role of the BMP6 protein in breast cancer and other types of cancer
Published in Growth Factors, 2021
Andrea Marlene García Muro, Azaria García Ruvalcaba, Lourdes del Carmen Rizo de la Torre, Josefina Yoaly Sánchez López
But, the role of BMP6 in cell lines proved to be interesting. Higher levels of BMP6 were found in the metastatic state and increased in cell migration (Joseph et al. 2012; Lu et al. 2017; Darby et al. 2008) and were associated with an EMT phenotype increment, bone metastases and faster progression also confirming the BMP6 participation in drug resistance when transcriptionally induced by phospholipase C (PLCɛ) (Yuan et al. 2019). The relationship of BMP6 with androgen receptor expression and cell proliferation (Yang et al. 2014) in the absence of androgens, WNT5A stimulated the expression of BMP6 and, successively, BMP6 increased cell proliferation, the authors confirmed the physical interaction of Smad 5 and β-catenin and their joint nuclear translocation in this pathway (Lee et al. 2014).
The molecular basis of platelet biogenesis, activation, aggregation and implications in neurological disorders
Published in International Journal of Neuroscience, 2020
Abhilash Ludhiadch, Abhishek Muralidharan, Renuka Balyan, Anjana Munshi
ADP activates platelets through 3 purinergic receptors, namely P2Y1, P2Y12 and P2X1 which are responsible for platelet shape change, the release of thromboxane A2 and procoagulant activity. [54]. It also results in the intracellular mobilization of calcium. ADP also results in the binding of platelets to vitronectin and osteopontin which helps in the anchoring of platelets to disrupted plaques or injured vessel walls. It also plays an important role in inhibiting stimulated adenylate cyclase, activating phospholipase C and phospholipase A2 [55]. The exposure to sub-endothelial components results in the binding of specific platelet surface receptors to the platelets like the binding of collagen-specific surface glycoprotein Ia/IIa to collagen. von Willebrand factor (vWF) helps in the cross-bridging of platelets to one another or to the endothelial vessel walls via binding sites for extracellular matrix proteins and to platelet glycoprotein receptors GPIb and GPIIb-IIIa. They help in hemostasis by slowing down the platelets in circulation by crosslinking them with collagen or other ECM components. vWf is also important to hold or tether the platelets at the site of the injury even during high shear stress. The interaction of GPIba with vWf is very important for the tethering of platelets, at higher shear rates in arteries [56]. Fibrinogen has been proposed to play a significant role in the interaction of platelets with the walls of vessels especially at reduced shear rates, which is a characteristic of the circulation in veins [57].