Nitric oxide sets off an antioxidant response in adrenal cells: Involvement of sGC and Nrf2 in HO-1 induction

• Published in: Nitric oxide Vol. 37; pp. 1 - 10
• Main Authors: Astort, F., Mercau, M., Giordanino, E., Degese, M.S., Caldareri, L., Coso, O., Cymeryng, C.B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.02.2014
• Subjects: Adrenal Glands - cytology; Adrenal Glands - enzymology; Adrenal Glands - metabolism; Animals; Antioxidants - metabolism; Cells, Cultured; cGMP; Guanylate Cyclase - metabolism; Heme oxygenase 1; Heme Oxygenase-1 - metabolism; Mice; NF-E2-Related Factor 2 - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nuclear factor-erythroid 2-related factor (Nrf2); Solubility; Soluble guanylate cyclase; cGMP; Heme oxygenase 1; Nuclear factor-erythroid 2-related factor (Nrf2); Nitric oxide; Soluble guanylate cyclase
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2013.12.006

•DETA-NO stimulates transcription of HO-1gene in adrenal cells.•Induction of HO-1 by NO does not require the generation of oxidative stress.•HO-1 induction by NO involves the stimulation of Nrf2 transcriptional activity.•NO stimulation of sGC and cGMP triggers Nrf2 activation and HO-1 induction. 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.