Methylxanthines Modulate Circadian Period Length Independently of the Action of Phosphodiesterase

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dc.contributor.authorOlivares-Yañez, C.
dc.contributor.authorAlessandri, M.
dc.contributor.authorSalas, L.
dc.contributor.authorLarrondo, L.
dc.date.accessioned2024-09-11T13:28:27Z
dc.date.available2024-09-11T13:28:27Z
dc.date.issued2023-07
dc.descriptionTEXTO COMPLETO EN INGLÉS
dc.description.abstractEvidence from diverse organisms show that caffeine causes changes in the circadian clock, causing period lengthening. The fungus Neurospora crassa is no exception; here, several methylxanthines such as caffeine, theophylline, and aminophylline cause period lengthening in a concentration-dependent manner. ABSTRACT In Neurospora crassa, caffeine and other methylxanthines are known to inhibit phosphodiesterase (PDE) activity, leading to augmented cAMP levels. In this organism, it has also been shown that the addition of these drugs significantly lengthens the circadian period, as seen by conidiation rhythms. Utilizing in vivo bioluminescence reporters, pharmacological inhibitors, and cAMP analogs, we revisited the effect of methylxanthines and the role of cAMP signaling in the Neurospora clockworks. We observed that caffeine, like all tested methylxanthines, led to significant period lengthening, visualized with both core-clock transcriptional and translational reporters. Remarkably, this phenotype is still observed when phosphodiesterase (PDE) activity is genetically or chemically (via 3-isobutyl-1-methylxanthine) abrogated. Likewise, methylxanthines still exert a period effect in several cAMP signaling pathway mutants, including adenylate cyclase (cr-1) and protein kinase A (PKA) (Δpkac-1) mutants, suggesting that these drugs lead to circadian phenotypes through mechanisms different from the canonical PDE-cAMP-PKA signaling axis. Thus, this study highlights the strong impact of methylxanthines on circadian period in Neurospora, albeit the exact mechanisms somehow remain elusive.
dc.description.urihttps://www-sciencedirect-com.recursosbiblioteca.unab.cl/org/science/article/pii/S2165049723006571
dc.identifier.citationMicrobiology Spectrum, Volume 11, Issue 4 , 5 July 2023
dc.identifier.doihttps://doi.org/10.1128/spectrum.03727-22
dc.identifier.issn2165-0497
dc.identifier.urihttps://repositorio.unab.cl/handle/ria/60069
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.rights.licenseAttribution 4.0 International
dc.subjectmethylxanthines
dc.subjectcircadian clock
dc.subjectphosphodiesterase
dc.subjectcAMP
dc.subjectprotein kinase A
dc.titleMethylxanthines Modulate Circadian Period Length Independently of the Action of Phosphodiesterase
dc.typeArtículo
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