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)

The sodium- and chloride-coupled glycine neurotransmitter transporters (GLYTs) control the availability of glycine at glycine-mediated synapses. The mainly glial GLYT1 is the key regulator of the glycine levels in glycinergic and glutamatergic pathways, whereas the neuronal GLYT2 is involved in the recycling of synaptic glycine from the inhibitory synaptic cleft. In this study, we report that stimulation of P2Y purinergic receptors with 2-methylthioadenosine 5'-diphosphate in rat brainstem/spinal cord primary neuronal cultures and adult rat synaptosomes leads to the inhibition of GLYT2 and the stimulation of GLYT1 by a paracrine regulation. These effects are mainly mediated by the ADP-preferring subtypes P2Y(1) and P2Y(13) because the effects are partially reversed by the specific antagonists N(6)-methyl-2'-deoxyadenosine-3',5'-bisphosphate and pyridoxal-5'-phosphate-6-azo(2-chloro-5-nitrophenyl)-2,4-disulfonate and are totally blocked by suramin. P2Y(12) receptor is additionally involved in GLYT1 stimulation. Using pharmacological approaches and siRNA-mediated protein knockdown methodology, we elucidate the molecular mechanisms of GLYT regulation. Modulation takes place through a signaling cascade involving phospholipase C activation, inositol 1,4,5-trisphosphate production, intracellular Ca(2+) mobilization, protein kinase C stimulation, nitric oxide formation, cyclic guanosine monophosphate production, and protein kinase G-I (PKG-I) activation. GLYT1 and GLYT2 are differentially sensitive to NO/cGMP/PKG-I both in brain-derived preparations and in heterologous systems expressing the recombinant transporters and P2Y(1) receptor. Sensitivity to 2-methylthioadenosine 5'-diphosphate by GLYT1 and GLYT2 was abolished by small interfering RNA (siRNA)-mediated knockdown of nitric-oxide synthase. Our data may help define the role of GLYTs in nociception and pain sensitization.
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PMID:P2Y purinergic regulation of the glycine neurotransmitter transporters. 2124 48

Cordycepin (3'-deoxyadenosine) is an adenosine analogue isolated from Cordyceps sinensis , which is a Chinese herbal medicine known to have many benefits, including adjustment of the physical condition, an anticancer effect, and enhancement of sexual performance. It was previously demonstrated that cordycepin could simultaneously activate steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells. However, the mechanism remains elusive. Thus, aim of the present study was to investigate the steroidogenic and apoptotic mechanism of cordycepin in MA-10 cells. MA-10 cells were treated with cordycepin at various dosages and time courses plus different protein kinase inhibitors. Steroid production, protein expression, and cell viability were then determined. Results illustrated that cordycepin stimulated MA-10 cell steroidogenesis in dose- and time-dependent relationships. However, cordycepin could not induce steroidogenic acute regulatory (StAR) protein expression. However, cordycepin did activate the phospholipase C/protein kinase C (PLC/PKC), but not PKA and PI3K, pathway to induce MA-10 cell steroidogenesis. Moreover, cordycepin could stimulate the phosphorylation of PKC, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (c-JNK), but not p38, in MA-10 cells. In addition, cordycepin could activate the PKC pathway to induce MA-10 cell death, and this death effect was not caused by cordycepin-stimulated progesterone from MA-10 cells. In conclusion, cordycepin stimulated intracellular PLC/PKC and MAPK signal transduction pathways to induce steroidogenesis and cell death in MA-10 mouse Leydig tumor cells.
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PMID:Cordycepin stimulated steroidogenesis in MA-10 mouse Leydig tumor cells through the protein kinase C Pathway. 2251 31


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