Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcineurin, a multifunctional Ca2+ (divalent cations)-dependent calmodulin-stimulated phosphoprotein phosphatase, has been reported to be present in the striatal neurons which project to the globus pallidus and the substantia nigra. In the present study, we examined what types of cells in the rat striatum express calcineurin. The calcineurin-positive neurons were of medium size (mean diameter of 16 microns) and constituted about 60-70% of the total neuronal population in the striatum. Under light microscopy, the calcineurin-positive neurons had round, triangular, or polygonal cell bodies with a relatively small amount of cytoplasm. Electron microscopic examination of 20 randomly selected striatal calcineurin-immunoreactive neurons revealed that their nuclei did not show any invaginations or intranuclear inclusions. The calcineurin-positive neurons were characterized by Golgi impregnation as the densely spinous type. On the other hand, it was demonstrated that calcineurin-positive neurons are a separate population from the diisopropylfluorophosphate-acetylcholinesterase-positive cells or nicotinamide adenine dinucleotide phosphate diaphorase-positive cells, by means of the combination of immunocytochemistry and enzyme histochemistry. In addition, simultaneous localization of calcineurin and substance P in a single cell was observed in some striatal neurons using a double immunostaining method. On the basis of these findings, it was considered that most calcineurin-immunoreactive neurons in the rat striatum may be classified as medium-size densely spiny neurons.
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PMID:Morphological characterization of the rat striatal neurons expressing calcineurin immunoreactivity. 244 61

Several evidence indicate that metabolic alterations play a pivotal role in cancer development. Here, we report that the mitochondrial uncoupling protein 2 (UCP2) sustains the metabolic shift from mitochondrial oxidative phosphorylation (mtOXPHOS) to glycolysis in pancreas cancer cells. Indeed, we show that UCP2 sensitizes pancreas cancer cells to the treatment with the glycolytic inhibitor 2-deoxy-D-glucose. Through a bidimensional electrophoresis analysis, we identify 19 protein species differentially expressed after treatment with the UCP2 inhibitor genipin and, by bioinformatic analyses, we show that these proteins are mainly involved in metabolic processes. In particular, we demonstrate that the antioxidant UCP2 induces the expression of hnRNPA2/B1, which is involved in the regulation of both GLUT1 and PKM2 mRNAs, and of lactate dehydrogenase (LDH) increasing the secretion of L-lactic acid. We further demonstrate that the radical scavenger N-acetyl-L-cysteine reverts hnRNPA2/B1 and PKM2 inhibition by genipin indicating a role for reactive oxygen species in the metabolic reprogramming of cancer cells mediated by UCP2. We also observe an UCP2-dependent decrease in mtOXPHOS complex I (NADH dehydrogenase), complex IV (cytochrome c oxidase), complex V (ATPase) and in mitochondrial oxygen consumption, suggesting a role for UCP2 in the counteraction of pancreatic cancer cellular respiration. All these results reveal novel mechanisms through which UCP2 promotes cancer cell proliferation with the concomitant metabolic shift from mtOXPHOS to the glycolytic pathway.
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PMID:The antioxidant uncoupling protein 2 stimulates hnRNPA2/B1, GLUT1 and PKM2 expression and sensitizes pancreas cancer cells to glycolysis inhibition. 2798 50