Nitric oxide: an inhibitor of NF-kappaB/Rel system in glial cells.
Nitric oxide (NO) has been reported to regulate NF-kappaB, 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-kappaB, its effect depending, among others, on the cell type considered. In this review, the inhibitory effect of NO on NF-kappaB (and subsequent suppression of NF-kappaB-dependent gene expression) in glial cells is reported. In particular, exogenous and endogenous NO has been observed to keep NF-kappaB suppressed, thus preventing the expression of NF-kappaB-induced genes, such as inducible NO synthase itself or HIV-1 long terminal repeat. Furthermore, the possible molecular mechanisms of NO-mediated NF-kappaB inhibition are discussed. More specifically, NO has been reported to suppress NF-kappaB activation inducing and stabilizing the NF-kappaB inhibitor, IkappaB-alpha. On the other hand, NO may inhibit NF-kappaB 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-kappaB in glial cells has been hypothesized.
Colasanti
M
M
Department of Biology, University of Roma Tre, Rome, Italy. colasant@uniroma3.it
Persichini
T
T
D000818:Animals; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000378:metabolism*
D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D014157:Transcription Factors; D051841:Transcription Factor RelB; D009569:Nitric Oxide