title: Nitric oxide sets off an antioxidant response in adrenal cells: involvement of sGC and Nrf2 in HO-1 induction.
abstract: Induction of microsomal heme oxygenase 1 (HO-1) activity is considered a cytoprotective mechanism in different cell types. In adrenal cells, HO-1 induction by ACTH exerts a modulatory effect on steroid production as well. As nitric oxide (NO) has been also regarded as an autocrine/paracrine modulator of adrenal steroidogenesis we sought to study the effects of NO on the induction of HO-1 and the mechanism involved. We hereby analyzed the time and dose-dependent effect of a NO-donor (DETA/NO) on HO-1 induction in a murine adrenocortical cell line. We showed that this effect is mainly exerted at a transcriptional level as it is inhibited by actinomycin D and HO-1 mRNA degradation rates were not affected by DETA/NO treatment. HO-1 induction by NO does not appear to involve the generation of oxidative stress as it was not affected by antioxidant treatment. We also demonstrated that NO-treatment results in the nuclear translocation of the nuclear factor-erythroid 2-related factor (Nrf2), an effect that is attenuated by transfecting the cells with a dominant negative isoform of Nrf2. We finally show that the effects of the NO-donor are reproduced by a permeable analog of cGMP and that a soluble guanylate cyclase specific inhibitor blocked both the induction of HO-1 by NO and the nuclear translocation of Nrf2.
authors.affiliation: Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, CEFYBO-CONICET, Argentina. Electronic address: pacoastort@gmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Astort
authors.affiliation: Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, CEFYBO-CONICET, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Mercau
authors.affiliation: Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, CEFYBO-CONICET, Argentina.
authors.forename: E
authors.initials: E
authors.lastname: Giordanino
authors.affiliation: LFBM-DFBMC, Departamento de Fisiología y Biología Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
authors.forename: M S
authors.initials: MS
authors.lastname: Degese
authors.affiliation: Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, CEFYBO-CONICET, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Caldareri
authors.affiliation: LFBM-DFBMC, Departamento de Fisiología y Biología Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
authors.forename: O
authors.initials: O
authors.lastname: Coso
authors.affiliation: Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, CEFYBO-CONICET, Argentina.
authors.forename: C B
authors.initials: CB
authors.lastname: Cymeryng
mesh_terms: D000311:Adrenal Glands / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D006162:Guanylate Cyclase / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D012995:Solubility
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D009569:Nitric Oxide; D051547:Heme Oxygenase-1; D006162:Guanylate Cyclase
keywords: Heme oxygenase 1; Nitric oxide; Nuclear factor-erythroid 2-related factor (Nrf2); Soluble guanylate cyclase; cGMP