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)

Fructose-1,6-diphosphate (FDP) is a physiological product which exhibits pharmacological properties. This study shows that FDP (1-3 mM) inhibits platelet aggregation induced by the agonists thrombin, vasopressin, platelet activating factor, ADP, adrenaline, arachidonate and the stable thromboxane analogue U 44069. Thrombin-promoted ATP secretion and cytosolic Ca2+ rise are also drastically inhibited by FDP, which decreases, although to a lesser extent, the protein kinase C-dependent phosphorylation of the 47 kDa protein. The inhibition on thrombin-induced aggregation is shared, albeit less efficiently, by glucose-1,6-diphosphate and fructose-2,6-diphosphate but not by other phosphorylated monosaccharides (fructose-1:2 cyclic,6-diphosphate, glucose-1- and glucose-6-phosphate, fructose-1- and fructose-6-phosphate, mannose-6-phosphate and 5-phosphoryl ribose-1-pyrophosphate). FDP does not affect platelet activation induced by the protein kinase C activators dioctanoylglycerol or phorbol 12-myristate 13-acetate. No increase of cAMP concentration is observed in FDP-treated platelets. Altogether, these results indicate that FDP inhibits platelet activation at a level preceding phospholipase C. The data are consistent with a general inhibitory action of FDP on signal transmission.
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PMID:Fructose-1,6-diphosphate inhibits platelet activation. 131 5

The mechanism by which glucose recognition of B cells results in the release of inositol 1,4,5-trisphosphate is not known at present. In pancreatic islets, fructose shares a common metabolic pathway with glucose from the second step of glycolysis and can augment insulin secretion at stimulatory glucose levels. To evaluate the impact of glycolysis on the release of inositol 1,4,5-trisphosphate, we studied the effect of glucose and fructose metabolism on insulin secretion and the activation of inositol-specific phospholipase C, using collagenase digested rat pancreatic islets incorporated with 3H-labelled myo-inositol. Inositol phosphates, generated by the cleavage of phosphatidyl inositol by inositol phospholipase C, were analyzed using fast protein liquid chromatography. The islets were exposed to 3.3, 5.5 and 12 mmol 1(-1) glucose for 45 min in the absence or presence of 10, 20 or 30 mmol 1(-1) fructose, and the amount of insulin released into the medium was measured. Intracellular inositol phosphate accumulation was measured under the same glucose concentrations with 0, 10 and 30 mmol 1(-1) fructose. As expected, fructose alone had no insulinotropic effect, but potentiated the glucose-induced (5.5 and 12 mmol 1(-1)) insulin secretion at concentrations of 10-30 mmol 1(-1). Glucose (12 vs. 3.3 mmol 1(-1)) significantly increased both intracellular content of inositol 1,4,5-trisphosphate, as well as its metabolite inositol 1,3,4-trisphosphate. Fructose, however, had no potentiating effects on the accumulation of inositol phosphates. It is therefore supposed that glucose does not activate inositol-specific phospholipase C via the glycolysis. Further, since fructose did not activate inositol-specific phospholipase C, this stimulation is likely to be induced by glucose as such.
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PMID:The effect of fructose metabolism on the accumulation of inositol phosphates in rat pancreatic islets. 874 5

The excitotoxic cascade may represent an important pathway leading to brain damage and cerebral palsy. Brain lesions induced in newborn mice by ibotenate (acting on N-methyl-D-aspartate receptors) and by S-bromowillardiine (acting on alpha-3-amino-hydroxy-5-methyl-4-isoxazole propionic acid and kainate receptors) mimic some aspects of white matter cysts and transcortical necrosis observed in human perinatal brain damage. Fructose 1,6-biphosphate (FBP) is a high-energy glycolytic pathway intermediate which, in therapeutic doses, is non-toxic and neuroprotective in hypoxic-ischemic models of brain injury. Mechanisms of action include modulation of intracellular calcium through phospholipase C (PLC) activation. The goal of this study was to determine the neuroprotective effects of FBP in a mouse model of neonatal excitotoxic brain injury. Mice that received intraperitoneal FBP had a significant reduction in size of ibotenate-induced (80% reduction) or S-bromowillardiine-induced (40% reduction) cortical plate lesions when compared with control animals. Studies of fragmented DNA and cleaved caspase 3 confirmed the survival promoting effects of FBP. FBP had no detectable effect on excitotoxic white matter lesions. The effects of FBP were antagonized by co-administration of PLC, protein kinase C or mitogen-associated protein kinase inhibitors but not by protein kinase A inhibitor. A moderate, transient cooling of pups immediately after the insult extended the therapeutic window for FBP, as FBP administered 24 h after ibotenate was still significantly neuroprotective in these pups. This data extends the neuroprotective profile of FBP in neonatal brain injury and identifies gray matter lesions involving N-methyl-D-aspartate receptors as a major target for this promising drug.
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PMID:Fructose-1,6-biphosphate prevents excitotoxic neuronal cell death in the neonatal mouse brain. 1258 34