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  Nitric oxide donors induce differentiation in a human catecholamine-rich cell line

Rodríguez-Martín, E., Casarejos, M., Bazan, E., Canals, S., Herranz, A., & Mena, M. (2000). Nitric oxide donors induce differentiation in a human catecholamine-rich cell line. Neuropharmacology, 39(11), 2090-2100. doi:10.1016/S0028-3908(00)00049-6.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-E432-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-AF4D-1
Genre: Journal Article

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Rodríguez-Martín, E, Author
Casarejos, MJ, Author
Bazan, E, Author
Canals, S1, Author              
Herranz, AS, Author
Mena, MA, Author
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1External Organizations, ou_persistent22              

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 Abstract: The nitric oxide (NO) donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), induced differentiation of human neuroblastoma NB69 cells to a dopamine phenotype, as shown by phase-contrast microscopy and tyrosine hydroxylase (TH) immunocytochemistry. NB69 cells were treated with 50 to 750 μM SNAP in serum-free-defined medium for 24 h. SNAP treatment did not increase the number of necrotic or apoptotic cells. However, a decrease in the number of viable cells was observed at 750 μM SNAP. In addition, a decrease in 3H-thymidine uptake was detected at the highest dose of SNAP. An increase in the antiapoptotic Bcl-2 and Bcl-xL protein levels and a decrease in the proapoptotic Bax and Bcl-xS protein levels were also detected by Western blot analysis after SNAP treatment. At low doses (50–125 μM), SNAP induced an increase in catecholamine levels, 3H-dopamine uptake, TH activity and monoamine metabolism, while a decrease in all these parameters was observed at high doses (250–750 μM). The TH protein content, analyzed by Western blot, remained unchanged in SNAP-treated cells throughout the range of doses studied, when compared with the control group. SNAP produced a dose-dependent decrease in the glutathione (GSH) content of the culture medium, without altering intracellular GSH. In addition, cGMP levels and nitrite concentration, measured in the supernatant of SNAP-treated cells, increased in a dose-dependent manner, as compared to control levels. The guanylate cyclase inhibitor lH-[1,2,4]oxadiazolo[4,3a]quinoxaline-l-one (ODQ) did not revert the SNAP-induced effect on 3H-dopamine uptake to control values. These results suggest that NO, released from SNAP, induces differentiation of NB69 cells and regulates TH protein at the post-transcriptional level through a cGMP-independent mechanism.

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 Dates: 2000-10
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/S0028-3908(00)00049-6
BibTex Citekey: 3319
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Title: Neuropharmacology
  Other : Neuropharmacol.
Source Genre: Journal
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Publ. Info: Amsterdam [etc.] : Pergamon
Pages: - Volume / Issue: 39 (11) Sequence Number: - Start / End Page: 2090 - 2100 Identifier: ISSN: 0028-3908
CoNE: https://pure.mpg.de/cone/journals/resource/954925428257