Circadian Regulation of Glutathione Levels and Biosynthesis in Drosophila melanogaster Public Deposited

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  • Circadian clocks generate daily rhythms in neuronal, physiological, and metabolic functions. Previous studies in mammals reported daily fluctuations in levels of the major endogenous antioxidant, glutathione (GSH), but the molecular mechanisms that govern such fluctuations remained unknown. To address this question, we used the model species Drosophila, which has a rich arsenal of genetic tools. Previously, we showed that loss of the circadian clock increased oxidative damage and caused neurodegenerative changes in the brain, while enhanced GSH production in neuronal tissue conferred beneficial effects on fly survivorship under normal and stress conditions. In the current study we report that the GSH concentrations in fly heads fluctuate in a circadian clock-dependent manner. We further demonstrate a rhythm in activity of glutamate cysteine ligase (GCL), the rate-limiting enzyme in glutathione biosynthesis. Significant rhythms were also observed for mRNA levels of genes encoding the catalytic (Gclc) and modulatory (Gclm) subunits comprising the GCL holoenzyme. Furthermore, we found that the expression of a glutathione S-transferase, GstD1, which utilizes GSH in cellular detoxification, significantly fluctuated during the circadian day. To directly address the role of the clock in regulating GSH-related rhythms, the expression levels of the GCL subunits and GstD1, as well as GCL activity and GSH production were evaluated in flies with a null mutation in the clock genes cycle and period. The rhythms observed in control flies were not evident in the clock mutants, thus linking glutathione production and utilization to the circadian system. Together, these data suggest that the circadian system modulates pathways involved in production and utilization of glutathione.
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  • Beaver LM, Klichko VI, Chow ES, Kotwica-Rolinska J, Williamson M, et al. (2012) Circadian Regulation of Glutathione Levels and Biosynthesis in Drosophila melanogaster. PLoS ONE 7(11): e50454. doi:10.1371/journal.pone.0050454
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  • description.provenance : Submitted by Deborah Campbell (deborah.campbell@oregonstate.edu) on 2013-02-20T23:11:11Z No. of bitstreams: 3 license_rdf: 22765 bytes, checksum: 56265f5776a16a05899187d30899c530 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) BeaverLauraMZoologyCircadianRegulationGlutathione.pdf: 993244 bytes, checksum: 2816d397de8f9b7ad56fdbd3c91aad03 (MD5)
  • description.provenance : Made available in DSpace on 2013-02-21T00:09:35Z (GMT). No. of bitstreams: 3 license_rdf: 22765 bytes, checksum: 56265f5776a16a05899187d30899c530 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) BeaverLauraMZoologyCircadianRegulationGlutathione.pdf: 993244 bytes, checksum: 2816d397de8f9b7ad56fdbd3c91aad03 (MD5) Previous issue date: 2012-11-30
  • description.provenance : Approved for entry into archive by Deborah Campbell(deborah.campbell@oregonstate.edu) on 2013-02-21T00:09:35Z (GMT) No. of bitstreams: 3 license_rdf: 22765 bytes, checksum: 56265f5776a16a05899187d30899c530 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) BeaverLauraMZoologyCircadianRegulationGlutathione.pdf: 993244 bytes, checksum: 2816d397de8f9b7ad56fdbd3c91aad03 (MD5)

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