Nitric oxide inhibits selectively the 17beta-estradiol-induced gene expression without affecting nongenomic events in HeLa cells.
17beta-Estradiol (E2) induces genomic (i.e., pC3-luciferase promoter-reporter construct expression) and nongenomic (i.e., DNA synthesis and IP(3) production) effects in HeLa cells only after transient transfection with the human estrogen receptor alpha (ERalpha) reporter plasmid. Here the effect of nitric oxide (NO) on both E2-induced effects in transiently transfected HeLa cells is reported. Remarkably, the E2-dependent gene transcription is inhibited dose-dependently by NO. By contrast, DNA synthesis and IP(3) production, representing nongenomic E2-dependent effects, are unaffected by NO. The selective NO action on E2-induced functions may be related to NO-mediated chemical modification(s) of the Cys residues present in the DNA recognition domain of ERalpha impairing DNA binding.
Marino
M
M
Department of Biology, University "Roma Tre,", Viale G. Marconi 446, Rome, I-00146, Italy. m.marino@bio.uniroma3.it
Ficca
R
R
Ascenzi
P
P
Trentalance
A
A
D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D017930:Genes, Reporter; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D043484:Proprotein Convertases; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D026422:S-Nitrosoglutathione; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
D047628:Estrogen Receptor alpha; D007295:Inositol Phosphates; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D009603:Nitroso Compounds; D011960:Receptors, Estrogen; D009569:Nitric Oxide; D004958:Estradiol; D026422:S-Nitrosoglutathione; D004247:DNA; C061872:FK 409; D043484:Proprotein Convertases; D016282:Aspartic Acid Endopeptidases; D005978:Glutathione