Redox and antioxidant modulation of circadian rhythms : Effects of nitroxyl, N-acetylcysteine and glutathione

Abstract: The circadian clock at the hypothalamic suprachiasmatic nucleus (SCN) entrains output rhythms to 24-h light cycles. To entrain by phase-advances, light signaling at the end of subjective night (circadian time 18, CT18) requires free radical nitric oxide (NO ) binding to soluble guanylate...

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Autores principales: Plano, Santiago Andrés, Baidanoff, Fernando Martín, Trebucq, Laura Lucía, Suárez, Sebastián Ángel, Doctorovich, Fabio, Golombek, Diego A., Chiesa, Juan José
Formato: Artículo
Lenguaje:Inglés
Publicado: Multidisciplinary Digital Publishing Institute 2021
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Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/11523
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spelling I33-R139-123456789-115232023-11-22T21:44:21Z Redox and antioxidant modulation of circadian rhythms : Effects of nitroxyl, N-acetylcysteine and glutathione Plano, Santiago Andrés Baidanoff, Fernando Martín Trebucq, Laura Lucía Suárez, Sebastián Ángel Doctorovich, Fabio Golombek, Diego A. Chiesa, Juan José SISTEMA NERVIOSO CENTRAL OXIDO NITRICO NUCLEO SUPRAQUIASMATICO MONOFOSFATO DE GUANOSINA CÍCLICO Abstract: The circadian clock at the hypothalamic suprachiasmatic nucleus (SCN) entrains output rhythms to 24-h light cycles. To entrain by phase-advances, light signaling at the end of subjective night (circadian time 18, CT18) requires free radical nitric oxide (NO ) binding to soluble guanylate cyclase (sGC) heme group, activating the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Phase-delays at CT14 seem to be independent of NO , whose redox-related species were yet to be investigated. Here, the one-electron reduction of NO nitroxyl was pharmacologically delivered by Angeli’s salt (AS) donor to assess its modulation on phase-resetting of locomotor rhythms in hamsters. Intracerebroventricular AS generated nitroxyl at the SCN, promoting phasedelays at CT14, but potentiated light-induced phase-advances at CT18. Glutathione/glutathione disulfide (GSH/GSSG) couple measured in SCN homogenates showed higher values at CT14 (i.e., more reduced) than at CT18 (oxidized). In addition, administration of antioxidants N-acetylcysteine (NAC) and GSH induced delays per se at CT14 but did not affect light-induced advances at CT18. Thus, the relative of NO nitroxyl generates phase-delays in a reductive SCN environment, while an oxidative favors photic-advances. These data suggest that circadian phase-locking mechanisms should include redox SCN environment, generating relatives of NO , as well as coupling with the molecular oscillator. 2021-05-13T14:22:55Z 2021-05-13T14:22:55Z 2021 Artículo Plano, S. A., Baidanoff, F. M., Trebucq, L.L., Suarez, S.Á., Doctorovich, F., Golombek, D.A., Chiesa, J.J. Redox and antioxidant modulation of circadian rhythms : Effects of nitroxyl, N-acetylcysteine and glutathione [en línea]. Molecules 2021, 26(2514). Doi: 10.3390/ molecules26092514. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/11523 1420-3049 https://repositorio.uca.edu.ar/handle/123456789/11523 10.3390/ molecules26092514 33925826 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Multidisciplinary Digital Publishing Institute Molecules 2021, 26(2514)
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic SISTEMA NERVIOSO CENTRAL
OXIDO NITRICO
NUCLEO SUPRAQUIASMATICO
MONOFOSFATO DE GUANOSINA CÍCLICO
spellingShingle SISTEMA NERVIOSO CENTRAL
OXIDO NITRICO
NUCLEO SUPRAQUIASMATICO
MONOFOSFATO DE GUANOSINA CÍCLICO
Plano, Santiago Andrés
Baidanoff, Fernando Martín
Trebucq, Laura Lucía
Suárez, Sebastián Ángel
Doctorovich, Fabio
Golombek, Diego A.
Chiesa, Juan José
Redox and antioxidant modulation of circadian rhythms : Effects of nitroxyl, N-acetylcysteine and glutathione
topic_facet SISTEMA NERVIOSO CENTRAL
OXIDO NITRICO
NUCLEO SUPRAQUIASMATICO
MONOFOSFATO DE GUANOSINA CÍCLICO
description Abstract: The circadian clock at the hypothalamic suprachiasmatic nucleus (SCN) entrains output rhythms to 24-h light cycles. To entrain by phase-advances, light signaling at the end of subjective night (circadian time 18, CT18) requires free radical nitric oxide (NO ) binding to soluble guanylate cyclase (sGC) heme group, activating the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Phase-delays at CT14 seem to be independent of NO , whose redox-related species were yet to be investigated. Here, the one-electron reduction of NO nitroxyl was pharmacologically delivered by Angeli’s salt (AS) donor to assess its modulation on phase-resetting of locomotor rhythms in hamsters. Intracerebroventricular AS generated nitroxyl at the SCN, promoting phasedelays at CT14, but potentiated light-induced phase-advances at CT18. Glutathione/glutathione disulfide (GSH/GSSG) couple measured in SCN homogenates showed higher values at CT14 (i.e., more reduced) than at CT18 (oxidized). In addition, administration of antioxidants N-acetylcysteine (NAC) and GSH induced delays per se at CT14 but did not affect light-induced advances at CT18. Thus, the relative of NO nitroxyl generates phase-delays in a reductive SCN environment, while an oxidative favors photic-advances. These data suggest that circadian phase-locking mechanisms should include redox SCN environment, generating relatives of NO , as well as coupling with the molecular oscillator.
format Artículo
author Plano, Santiago Andrés
Baidanoff, Fernando Martín
Trebucq, Laura Lucía
Suárez, Sebastián Ángel
Doctorovich, Fabio
Golombek, Diego A.
Chiesa, Juan José
author_facet Plano, Santiago Andrés
Baidanoff, Fernando Martín
Trebucq, Laura Lucía
Suárez, Sebastián Ángel
Doctorovich, Fabio
Golombek, Diego A.
Chiesa, Juan José
author_sort Plano, Santiago Andrés
title Redox and antioxidant modulation of circadian rhythms : Effects of nitroxyl, N-acetylcysteine and glutathione
title_short Redox and antioxidant modulation of circadian rhythms : Effects of nitroxyl, N-acetylcysteine and glutathione
title_full Redox and antioxidant modulation of circadian rhythms : Effects of nitroxyl, N-acetylcysteine and glutathione
title_fullStr Redox and antioxidant modulation of circadian rhythms : Effects of nitroxyl, N-acetylcysteine and glutathione
title_full_unstemmed Redox and antioxidant modulation of circadian rhythms : Effects of nitroxyl, N-acetylcysteine and glutathione
title_sort redox and antioxidant modulation of circadian rhythms : effects of nitroxyl, n-acetylcysteine and glutathione
publisher Multidisciplinary Digital Publishing Institute
publishDate 2021
url https://repositorio.uca.edu.ar/handle/123456789/11523
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