Cvetkovic, I. (56186289000)I. (56186289000)CvetkovicPopadic, D. (6602255798)D. (6602255798)PopadicVuckovic, O. (6603047659)O. (6603047659)VuckovicHarhaji, Lj. (6507652139)Lj. (6507652139)HarhajiMiljkovic, Dj. (7006524033)Dj. (7006524033)MiljkovicTrajkovic, V. (7004516866)V. (7004516866)Trajkovic2025-07-022025-07-022004https://doi.org/10.1016/j.brainres.2003.11.014https://www.scopus.com/inward/record.uri?eid=2-s2.0-0346023052&doi=10.1016%2fj.brainres.2003.11.014&partnerID=40&md5=4d9fefa7834f1065e81f90d2eea20e27https://remedy.med.bg.ac.rs/handle/123456789/14398The 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-γ, TNF-α, IL-1)-triggered NO synthesis in a time- and dose-dependent manner. In contrast, 5-AzadC did not potentiate NO production in IFN-γ-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-γ-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. © 2003 Elsevier B.V. All rights reserved.5-Aza-2′-deoxycytidineAstrocyteiNOSNitric oxide