Role of G-substrate in the NO/cGMP/PKG signal transduction pathway for photic entrainment of the hamster circadian clock

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Abstract: The mammalian circadian clock at the hypothalamic suprachiasmatic nuclei (SCN) entrains biological rhythms to the 24- h cyclic environment, by encoding light-dark transitions in SCN neurons. Light pulses induce phase shifts in the clock and in circadian rhythms; photic signaling for circ...

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Autores principales: Plano, Santiago Andrés, Alessandro, María Soledad, Trebucq, Laura Lucía, Endo, Shogo, Golombek, Diego A., Chiesa, Juan José
Formato: Artículo
Lenguaje:Inglés
Publicado: SAGE Publishing 2021
Materias:
NUCLEO SUPRAQUIASMATICO
PROTEíNA FOSFATASA 2A
SISTEMA NERVIOSO CENTRAL
LUZ
RITMO CIRCADIANO
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/11524
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-11524
record_format dspace
spelling I33-R139-123456789-115242023-11-22T21:45:24Z Role of G-substrate in the NO/cGMP/PKG signal transduction pathway for photic entrainment of the hamster circadian clock Plano, Santiago Andrés Alessandro, María Soledad Trebucq, Laura Lucía Endo, Shogo Golombek, Diego A. Chiesa, Juan José NUCLEO SUPRAQUIASMATICO PROTEíNA FOSFATASA 2A SISTEMA NERVIOSO CENTRAL LUZ RITMO CIRCADIANO Abstract: The mammalian circadian clock at the hypothalamic suprachiasmatic nuclei (SCN) entrains biological rhythms to the 24- h cyclic environment, by encoding light-dark transitions in SCN neurons. Light pulses induce phase shifts in the clock and in circadian rhythms; photic signaling for circadian phase advances involves a nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) pathway, increasing the expression of Period (Per) genes. Effectors downstream of PKG remain unknown. Here we investigate the role of G-substrate (GS), a PKG substrate, in the hamster SCN. GS and phosphorylated G-substrate (p-GS) were present in a subset of SCN cells. Moreover, GS phosphorylation (p- GS/GS ratio) increased in SCN homogenates after light pulses delivered at circadian time (CT) 18 and intraperitoneal treatment with sildenafil, an inhibitor of phosphodiesterase 5 (a cGMP-specific phosphodiesterase). On the other hand, intracerebroventricular treatment with the PKG inhibitor KT5823, reduced photic phosphorylation of GS to basal levels. Since p-GS could act as a protein phosphatase 2 A (PP2A) inhibitor, we demonstrated physical interaction between p-GS and PP2A in SCN homogenates, and also a light-pulse dependent decrease of PP2A activity. Intracerebroventricular treatment with okadaic acid, a PP2A inhibitor, increased the magnitude of light-induced phase advances of locomotor rhythms. We provide evidence on the physiological phosphorylation of GS as a new downstream effector in the NO/cGMP/PKG photic pathway in the hamster SCN, including its role as a PP2A inhibitor. 2021-05-13T15:28:58Z 2021-05-13T15:28:58Z 2021 Artículo Plano, S. A., Alessandro, M. S., Trebucq, L. L., Endo, S., Golombek, D. A., Chiesa, J. J. Role of G-substrate in the NO/cGMP/PKG signal transduction pathway for photic entrainment of the hamster circadian clock [en línea]. American Society for Neurochemistry. 2021, 13(1-12). Doi: 10.1177/1759091420984920. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/11524 1759-0914 (on line) https://repositorio.uca.edu.ar/handle/123456789/11524 10.1177/1759091420984920 33430619 eng Atribución-NoComercial-CompartirIgual 4.0 Internacional http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf SAGE Publishing American Society for Neurochemistry. 2021, 13(1-12)
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic NUCLEO SUPRAQUIASMATICO
PROTEíNA FOSFATASA 2A
SISTEMA NERVIOSO CENTRAL
LUZ
RITMO CIRCADIANO
spellingShingle NUCLEO SUPRAQUIASMATICO
PROTEíNA FOSFATASA 2A
SISTEMA NERVIOSO CENTRAL
LUZ
RITMO CIRCADIANO
Plano, Santiago Andrés
Alessandro, María Soledad
Trebucq, Laura Lucía
Endo, Shogo
Golombek, Diego A.
Chiesa, Juan José
Role of G-substrate in the NO/cGMP/PKG signal transduction pathway for photic entrainment of the hamster circadian clock
topic_facet NUCLEO SUPRAQUIASMATICO
PROTEíNA FOSFATASA 2A
SISTEMA NERVIOSO CENTRAL
LUZ
RITMO CIRCADIANO
description Abstract: The mammalian circadian clock at the hypothalamic suprachiasmatic nuclei (SCN) entrains biological rhythms to the 24- h cyclic environment, by encoding light-dark transitions in SCN neurons. Light pulses induce phase shifts in the clock and in circadian rhythms; photic signaling for circadian phase advances involves a nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) pathway, increasing the expression of Period (Per) genes. Effectors downstream of PKG remain unknown. Here we investigate the role of G-substrate (GS), a PKG substrate, in the hamster SCN. GS and phosphorylated G-substrate (p-GS) were present in a subset of SCN cells. Moreover, GS phosphorylation (p- GS/GS ratio) increased in SCN homogenates after light pulses delivered at circadian time (CT) 18 and intraperitoneal treatment with sildenafil, an inhibitor of phosphodiesterase 5 (a cGMP-specific phosphodiesterase). On the other hand, intracerebroventricular treatment with the PKG inhibitor KT5823, reduced photic phosphorylation of GS to basal levels. Since p-GS could act as a protein phosphatase 2 A (PP2A) inhibitor, we demonstrated physical interaction between p-GS and PP2A in SCN homogenates, and also a light-pulse dependent decrease of PP2A activity. Intracerebroventricular treatment with okadaic acid, a PP2A inhibitor, increased the magnitude of light-induced phase advances of locomotor rhythms. We provide evidence on the physiological phosphorylation of GS as a new downstream effector in the NO/cGMP/PKG photic pathway in the hamster SCN, including its role as a PP2A inhibitor.
format Artículo
author Plano, Santiago Andrés
Alessandro, María Soledad
Trebucq, Laura Lucía
Endo, Shogo
Golombek, Diego A.
Chiesa, Juan José
author_facet Plano, Santiago Andrés
Alessandro, María Soledad
Trebucq, Laura Lucía
Endo, Shogo
Golombek, Diego A.
Chiesa, Juan José
author_sort Plano, Santiago Andrés
title Role of G-substrate in the NO/cGMP/PKG signal transduction pathway for photic entrainment of the hamster circadian clock
title_short Role of G-substrate in the NO/cGMP/PKG signal transduction pathway for photic entrainment of the hamster circadian clock
title_full Role of G-substrate in the NO/cGMP/PKG signal transduction pathway for photic entrainment of the hamster circadian clock
title_fullStr Role of G-substrate in the NO/cGMP/PKG signal transduction pathway for photic entrainment of the hamster circadian clock
title_full_unstemmed Role of G-substrate in the NO/cGMP/PKG signal transduction pathway for photic entrainment of the hamster circadian clock
title_sort role of g-substrate in the no/cgmp/pkg signal transduction pathway for photic entrainment of the hamster circadian clock
publisher SAGE Publishing
publishDate 2021
url https://repositorio.uca.edu.ar/handle/123456789/11524
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