Nitric oxide:: An inhibitor of NF-κB/Rel system in glial cells

Nitric oxide (NO) has been reported to regulate NF-kappa B, one of the best-characterized transcription factors playing important roles in many cellular responses to a large variety of stimuli. NO has been suggested to induce or inhibit the activation of NF-kappa B, its effect depending, among others, on the cell type considered. In this review, the inhibitory effect of NO on NF-kappa B (and subsequent suppression of NF-kappa B-dependent gene expression) in glial cells is reported. In particular, exogenous end endogenous NO has been observed to keep NF-kappa B suppressed, thus preventing the expression of NF-kappa B-induced genes, such as inducible NO synthase itself or HIV-1 long terminal repeat. Furthermore, the possible molecular mechanisms of NO-mediated NF-kappa B inhibition are discussed. More specifically, NO has been reported to suppress NF-kappa B activation inducing and stabilizing the NF-kappa B inhibitor, I kappa B-alpha. On the other hand, NO may inhibit NF-kappa B DNA binding through S-nitrosylation of cysteine residue (i.e., Cys62) of the p50 subunit. As a whole, a novel concept that the balance of intracellular NO levels may control the induction of NF-kappa B in glial cells has been hypothesized. (C) 2000 Elsevier Science Inc.