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C Burgun

Publications and source records attributed to C Burgun.

10 recordsLinked to original sources
PubMed2000

Cyclic AMP-elevating agents induce the expression of MAP kinase phosphatase-1 in PC12 cells.

Stimulation of pheochromocytoma PC12 cells by cAMP-elevating agents caused the induction of the immediate early gene 3CH134, which encodes MAP kinase phosphatase-1 (MKP-1). Forskolin was as potent as serum in stimulating MKP-1 gene expression, whereas dibutyryl-cAMP and neuropeptide PACAP were less effective. Induction of the MKP-1 gene was accompanied by neo-synthesis of MKP-1 protein. MAP kinase activation was not involved in the cAMP-induced MKP-1 gene expression. The MAP kinase inactivation, that would result from MKP-1 induction in response to increased intracellular cAMP level, contributes to explain how hormones or neurotransmitters signaling through cAMP influence cell growth and differentiation.

Animals↗
PubMed1998

Cocaine and fluoxetine induce the expression of the hVH-5 gene encoding a MAP kinase phosphatase.

A novel class of immediate early genes that encode enzymes of the MAP kinase phosphatase family has recently been described. These enzymes are dual-specificity protein phosphatases and some show tissue-specific distribution, like the hVH-5 gene (homologue of vaccinia virus H1 phosphatase gene clone 5), which is expressed predominantly in the adult brain. In this paper, we investigated whether the hVH-5 gene is induced by psychostimulants in rat brain, as has been demonstrated for immediate early genes encoding transcription factors. Using in situ hybridization, we found that i.p. injection of cocaine, amphetamine and caffeine induced hVH-5 mRNA expression within 40 min in the nucleus accumbens (NAc), caudate putamen, frontal cortex and hippocampus, with a maximal effect in the NAc. The cocaine-induced hVH-5 gene induction involves the serotonergic system, since it was abolished in the NAc by lesioning serotonergic raphé projections with 5,7-dihydroxytryptamine. Moreover, the effect of cocaine was fully mimicked by the selective serotonin uptake inhibitor fluoxetine. In contrast to what has been described for c-fos and egr-1 immediate early genes, we found that hVH-5 mRNA expression in the NAc and hippocampus was as significant after repeated cocaine injections for 10 days as after a single injection. The considerable and prolonged induction of the MAP kinase phosphatase hVH-5 gene by psychostimulant drugs in postmitotic brain cells, particularly in the NAc, could indicate that MAP kinase substrates are involved in the reinforcing properties of drugs of abuse.

5,7-Dihydroxytryptamine↗
PubMed1997

5-Hydroxytryptamine induces TIS8/egr-1 and c-fos expression in PC12 cells. Involvement of tyrosine protein phosphorylation.

The TIS8/egr-1 gene is a member of the class of immediate early genes. Originally discovered as a mitogen-induced gene, it can also be induced by synaptic activity. We report here the induction of the TIS8/egr-1 gene by the neurotransmitter 5-hydroxytryptamine (5-HT) in cultured rat phaeochromocytoma PC12 cells. Induction was maximal 40 min after addition of 5-HT to the cells, and declined very rapidly to reach the basal level after 90 min. The electrophoretic mobility-shift assay showed that induction of the TIS8/egr-1 gene by 5-HT was accompained by increased Egr-1 protein binding to its DNA consensus sequence. We found an overall correlation of 5-HT-induced egr-1 expression with that of c-fos expression. The kinetics of the ability of both gene products to bind to their respective DNA consensus sequence was also similar. The 5-HT-induced activation in Egr-1 binding was inhibited by ketanserin and mesulergine, indicating that 5-HT exerted its action via a 5-HT2 receptor subtype. The tyrosine protein kinase inhibitor genistein abolished induction of the TIS8/egr-1 gene, suggesting that tyrosine kinase activity is required for the induction of early genes by 5-HT. Genistein also inhibited 5-HT-induced Egr-1 binding activity. The increase in phosphotyrosine content of focal adhesion kinase we noticed upon addition of 5-HT to cells suggests that this cytoplasmic tyrosine protein kinase mediates the effect of 5-HT in eliciting early gene induction.

Animals↗
PubMed1993

Reconstitution studies of lipid effects on insulin-receptor kinase activation.

Insulin receptors extracted from human placenta were reconstituted by dialysis into well-characterized lipid vesicles. For all types of lipids studied, vesicles were shown to be unilamellar, about 120 nm in diameter. The incorporation of lectin-purified insulin receptors was assessed by cosedimentation of 125I-insulin binding and [32P]phospholipids in a sucrose gradient. The insulin-binding activity was not modified by the composition of the lipid vesicles. However, tyrosine kinase activation appeared to be more sensitive to its lipid environment. Mixtures of phosphatidylcholine/phosphatidylserine or phospholipids/phosphatidylserine, in ratios of 1-4, increased the insulin-induced tyrosine kinase activation in a dose-dependent manner. In contrast, experiments performed in the presence of phosphatidylinositol showed a decrease in the enzyme stimulation. These results indicate an opposing involvement of these two anionic phospholipids in the kinase activation. Inclusion of cholesterol (10-30%) into phosphatidylcholine vesicles reduced kinase activation, which was drastically inhibited by 30% cholesterol. The effect of a total extract of brain gangliosides was biphasic, stimulatory at low concentration (5-10%), but with a reverse effect at higher concentrations. These results stress the importance of the lipid environment for insulin-receptor signaling, particularly for the insulin-induced activation of its beta-subunit kinase.

Animals↗
PubMed1991

Depolarization produces an acidification of adrenal gland perfusates.

Stimulation of adrenal glands with a variety of agonists or high potassium produced an acidification of the perfusion medium. The magnitude of the transient pH decrease was similar to that found in other nervous structures, and depended on the buffering capacity of the perfusion medium. However, no alkaline transient could be detected in this tissue. This acidification required Ca2+ and occurred under conditions producing catecholamine release. Since firstly the acidification could not be directly correlated with the amount of catecholamine released and secondly the time-course of both phenomena was different, suggesting that the acidification did not only result from the exocytosis of the acidic content of the chromaffin vesicles. The extracellular acidification may in addition originate: (a) partly from the proton release from acidic proteins, (b) from an output of acid equivalents from the cytoplasmic medium, either by the Na+/H+ antiporter present in all animal cells [24], or another mechanism yet to be determined.

Acetylcholine↗
PubMed1991

pH-induced reorganization of synaptic membrane as revealed by fluorescence anisotropy and energy transfer.

Two fluorescent probes, 2-(9-anthroyloxy)stearate and 12-(9-anthroyloxy)stearate, were used to investigate the effects of the neutralization of membrane charges on the organization of synaptic plasma membrane. Steady state fluorescence anisotropy measurements showed that a pH decrease provoked a rigidification of the synaptic membrane surface, whereas the bilayer core remained unaffected. The same effect was observed with negatively charged lipid vesicles. The relative distribution of proteins and the probes was estimated by fluorescence energy transfer from protein tryptophans to fluorescent probes: a pH decrease provoked an increase of the energy transfer, which was most pronounced with the surface probe, indicating an average closer packing between proteins and the probes. The modifications induced by a pH decrease were temperature dependent and were most marked at low temperatures. The results suggest that neutralization of the membrane charges provoked a redistribution of both membrane lipids and proteins. These findings are discussed in terms of a heterogeneous distribution of these membrane components.

Animals↗
PubMed1985

Osmotic fragility of chromaffin granules prepared under isoosmotic or hyperosmotic conditions and localization of acetylcholinesterase.

In chromaffin cells of the adrenal medulla, catecholamines are stored in secretory granules. Different methods have been described to purify chromaffin granules. In the present study, storage granules were prepared using isoosmotic self-generating Percoll gradients or hyperosmotic sucrose gradients, and a comparison of their physical properties in response to osmotic changes was made. Catecholamines, dopamine beta-hydroxylase activity and protein were detected both in the external medium and in the granule fraction according to the medium osmolality. Suspension turbidity was used as a measure of organelle integrity. Acetylcholinesterase activity was found to be associated with both isoosmotically and hyperosomotically prepared granules. The total acetylcholinesterase activity was determined after adding Triton X-100 to the assay medium. When adrenal medullary tissue was homogenized in buffers containing echothiopate, an inhibitor of acetylcholinesterase, only 15-20% of enzyme activity was inhibited, excluding the possibility that main granule acetylcholinesterase could be due to contamination by plasma membrane fragments, endoplasmic reticulum and Golgi membranes. When granules were suspended in hypoosmotic buffers, a soluble acetylcholinesterase form was released into the external medium, while an insoluble acetylcholinesterase form was still found associated with the membrane fraction. Soluble acetylcholinesterase was found to be released differently than soluble dopamine beta-hydroxylase, indicating that acetylcholinesterase may be associated with a more osmotically resistant granule population.

Acetylcholinesterase↗
PubMed1980

Influence of acetylcholine on rebinding of soluble acetylcholinesterase to a synaptosomal fraction from rat brain.

Acetylcholinesterase (Acetylcholine acetylhydrolase E.C. 3.1.1.7.) released from a rat brain synaptosomal fraction was shown to rebind upon incubation in the presence of 3 mM acetylcholine. This action was shown to be reversible. Glutamate, aspartate and gamma-aminobutyrate antagonise this effect. Solubilization of both bulk protein and acetylcholinesterase by Lubrol WX and triton X 100 after acetylcholine incubation of synaptosomal fractions is much lower than in the non incubated preparation. Local production of protons due to the hydrolysis of acetylcholine by the enzyme could partially explain the reassociation of the enzyme. We suggest that the observed phenomenon may play some physiological role in the function of acetylcholinesterase.

Acetylcholine↗