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Título : Role of G-substrate in the NO/cGMP/PKG signal transduction pathway for photic entrainment of the hamster circadian clock
Autor : Plano, Santiago Andrés 
Alessandro, María Soledad 
Trebucq, Laura Lucía 
Endo, Shogo 
Golombek, Diego A. 
Chiesa, Juan José 
Fecha de publicación : 2021
Editorial : SAGE Publishing
Cita : 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:
Resumen : 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.
ISSN : 1759-0914 (on line)
Disciplina: MEDICINA
DOI: 10.1177/1759091420984920
Derechos: Atribución-NoComercial-CompartirIgual 4.0 Internacional
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