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

Nitric Oxide : Biology and Chemistry
Francisco AstortCora B Cymeryng

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 bl...Continue Reading

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Citations

Jul 15, 2016·Journal of Molecular Endocrinology·F AstortC B Cymeryng
Apr 11, 2018·Antioxidants & Redox Signaling·Veena SomasundaramDavid A Wink
Apr 23, 2016·Environmental Science and Pollution Research International·Marwa Ahmed AbassHebatallah Husseini Atteia
May 4, 2018·Neural Regeneration Research·Jonathan M Borkum

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