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Different sensitivity of neurons and neuroblastoma cells to quercetin treatment

100%
Jakubowicz-Gil J., Rzeski W., Zdzisinska B., Piersiak T., Weiksza K., Glowniak K., Gawron A.
Acta Neurobiologiae Experimentalis
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2008
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vol. 68
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issue 4
463-476
EN
determined the sensitivity of neurons and neuroblastoma cells on apoptosis and necrosis induction upon quercetin treatment. No expression of Hsp72 was observed in neurons, which were more sensitive to cell death upon quercetin treatment than neuroblastoma cells, where Hsp72 expression was observed. Reduction of Hsp72 gene expression in neuroblastoma cells by antisense oligonucleotides made them more sensitive to pro-apoptotic action of quercetin. Moreover, the flavonoid decreased Hsp27, procaspase-3, MRP and PKB expression in neuroblastoma cells and in neurons. Nuclear localization of mainly cytoplasmic Hsp27 was observed in neuroblastoma cells after treatment with high quercetin concentrations, while in neurons, the protein was present in nuclei both in control and quercetin treated cells. Our results suggest that quercetin induce apoptosis more effectively in cells with low level of Hsp 72 expression. Higher sensitivity of neurons for cell death after treatment with high quercetin concentrations in comparison to neuroblastoma cell line should also be taken into consideration in further studies on using studied flavonoid as therapeutic agent.
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Sphingosylphosphorylcholine induces mitochondria-mediated apoptosis in neuro 2a cells: Involvement of protein kinase C

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Miguel B. G., Fernandez I., Toboso I., Agudo-Lopez A., Catalan E., Martinez A. M.
Acta Neurobiologiae Experimentalis
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2008
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vol. 68
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issue 4
443-452
EN
We demonstrate that sphingosylphosphorylcholine-mediated cell death involves the activation of different protein kinase C isozymes in different manners. Treating cells with sphingosylphosphorylcholine resulted in activation of protein kinase C delta, which is necessary, together with elevation of Ca2+, for sphingosylphosphorylcholine-induced apoptosis. A rapid translocation from cytosol to membrane, and a proteolytic protein kinase C delta cleavage was found, probably due to activation of caspase-3, to give a catalytically active fragment involved in cellular apoptosis. Moreover, sphingosylphosphorylcholine also induced translocation of protein kinase C zeta, resulting in an anti-apoptotic effect. To explore whether a mitochondrial pathway is involved in sphingosylphosphorylcholine-induced apoptosis, we analyzed the effect of sphingosylphosphorylcholine on cytochrome c release and caspase-3 activity. We must point out that the sphingolipid caused an increase of cytochrome c release from mitochondria to cytosol concomitantly with an increase of caspase-3 activity. Furthermore, a translocation of Bax was found, after sphingosylphosphorylcholine treatment.
3

Correlation between N-myc amplification and other prognostic markers in children with neuroblastoma

100%
Januszkiewicz-Lewandowska D.
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4
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Carnitine - a known compound, a novel function in neural cells

75%
Nalecz K., Nalecz M.
Acta Neurobiologiae Experimentalis
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1996
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vol. 56
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issue 2
597-609
EN
Carnitine (4-N-trimethylammonium-3-hydroxybutyric acid) seems to fullfil in the brain a different role than in peripheral tissues.Carnitine is accumulated by neural cells in a sodium-dependent way.The existence of a novel rtansporter in plasma membrane, specific to compounds with a polar group in the beta-position with respect to carboxyl group, has been postulated.The presence of carnitine carrier in the inner mitochondrial membrane has been proven and the protein has been purified.It is postulated that its major role in adult brain would be rtanslocation of acetyl moieties from mitochondria into the cytoplas for acetylocholine synthesis.The latter process is stimulated by carnitine and choline in a synergistic way in cells utilizing glucose as a main energetic substrate.Carnitine metabolism in neural cells leads to accumulation of different acyl derivatives of carnitine.Palmitoylcarnitine can influence directly the activity of protein kinase C.An involvment of carnitine in a decrease of palmitate pool used for palmitoylation of regulatory proteins has been postulated.
5
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Effect of opioids on Ca2+/cAMP responsive element binding protein

75%
Bilecki W., Przewlocki P. R., Przewlocki R.
Acta Neurobiologiae Experimentalis
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2000
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vol. 60
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issue 4
557-567
EN
Ca2+/cAMP response element binding protein (CREB) is an important factor linking the opioid-regulated secondary messenger systems to alterations in gene expression. Opioids regulate CREB level, its phosphorylation and binding to its corresponding response element in the promoters of several genes implicated in drug addiction. CREB mediates the action of opioids on the expression of several genes in brain regions responsible for drug-seeking behavior and manifestation of signs of dependence. Moreover, alterations in CREB level can affect the rewarding properties of morphine and regulate the self-administration of cocaine. At the cellular level CREB acts as convergence point for different cellular pathways. Opioids affect two different intracellular mediator systems: inhibitory - connected with cAMP, and stimulatory - involving calcium and the PKC pathway. Both can affect CREB but in different phases of opiate action. The presence of this biphasic mechanism can explain the phenomenon of the induction of some CRE-controlled genes after both acute and chronic morphine administration. Cellular studies also highlight the relevance of other ATF/CREB family members which can affect Ca2+/cAMP response element (CRE) controlled transcription as well as other transcription factors which make the opioid induction longer lasting.
6
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Effect of palmitoylcarnitine on the cellular differentiation, proliferation and protein kinase C activity in neuroblastoma nb-2a

75%
Nalecz K. A., Mroczkowska J. E., Berent U., Nalecz M. J.
Acta Neurobiologiae Experimentalis
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1997
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vol. 57
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issue 4
263-274
EN
Palmitoylcarnitine is synthesized through the action of palmitoylcarnitine transferase I - an enzyme specifically inhibited by etomoxir. An increase of the intracellular content of palmitoylcarnitine in neuroblastoma NB-2a cells after administration of carnitine was correlated with an inhibition of cell proliferation and a concomitant promotion of differentiation processes. The activity of protein kinase C was measured in vivo, with cells permeabilized through the use of streptolysin O and a peptide substrate. Palmitoylcarnitine inhibited the phorbol ester stimulated reaction of the peptide phosphorylation in a concentration dependent way. The degree of protein kinase C inhibition was correlated with intracellular increase of the palmitoylcarnitine content, pointing to this compound as a natural modulator of protein kinase C activity.
7
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Isulfhydryl reagents with K+ transport in adrenal chromaffin granules

63%
Szewczyk A., Lobanov N. A., Nowotny M., Nalecz M. J., Berent U., Mroczkowska J. E., Nalecz K. A.
Acta Neurobiologiae Experimentalis
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1997
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vol. 57
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issue 4
329-332
EN
In the present study the functional role of SH groups in the Ca2+ -independent K+ selective channel activity in the membrane of bovine adrenal gland chromaffin granules has been studied. Ionic channel activity has been estimated using 86Rb+, a K+ analogue, flux measurements. The inhibition of chromaffin granules K+ channel by SH modifying agents, such as N ethylmaleimide, mersalyl and phenylarsenoxide, is described.
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