5-Aza-2'-deoxycytidine stimulates inducible nitric oxide synthase induction in C6 astrocytoma cells
2004
Аутори:
Stojanović, Ivana D.Popadić, Dušan
Vučković, Olivera
Harhaji-Trajković, Ljubica
Miljković, Đorđe
Trajković, Vladimir
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2003 Elsevier B.V.
Метаподаци
Приказ свих података о документуАпстракт:
The influence of a nucleoside analog 5-aza-2'-deoxycytidine (5-AzadC) on inducible nitric oxide synthase (iNOS)-dependent nitric oxide (NO) production in various rat cell types was investigated. In C6 astrocytoma cell line and primary astrocytes, 5-AzadC enhanced proinflammatory cytokine (IFN-gamma, TNF-alpha, IL-1)-triggered NO synthesis in a time- and dose-dependent manner. In contrast, 5-AzadC did not potentiate NO production in IFN-gamma-stimulated macrophages, fibroblasts, or endothelial cells. Blockade of transcription or translation in C6 cells abolished the observed effect, suggesting the iNOS gene expression, rather than its catalytic activity, as a target for the drug action. Accordingly, 5-AzadC upregulated IFN-gamma-induced expression of iNOS mRNA in C6 astrocytes. The effect of 5-AzadC on astrocyte NO release was blocked by the inhibitor of p44/42 mitogen activated protein kinase-dependent signaling. Finally, the observed stimulatory effect of 5-AzadC on iNOS expression was apparently independent of DNA demethylation, as DNA digestion with methylation-sensitive restriction enzyme HpaII showed that 5-AzadC failed to demethylate cellular DNA in conditions used for iNOS induction.
Кључне речи:
5-Aza-2V -deoxycytidine; Astrocyte; Nitric oxide; iNOSИзвор:
Brain Research, 2004, 998, 1, 83-90Финансирање / пројекти:
- The Ministry of Science, Technology and Development of The Republic of Serbia (Grants No. 1664 and No. 2020)
DOI: 10.1016/j.brainres.2003.11.014
ISSN: 0006-8993
PubMed: 14725971