Article
 

Circadian Regulation of Glutathione Levels and Biosynthesis in Drosophila melanogaster

公开 Deposited

可下载的内容

下载PDF文件
https://ir.library.oregonstate.edu/concern/articles/8w32r6736

Descriptions

Attribute NameValues
Creator
Abstract
  • 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.
License
Resource Type
DOI
Date Available
Date Issued
Citation
  • Beaver LM, Klichko VI, Chow ES, Kotwica-Rolinska J, Williamson M, Orr WC, et al. (2012) Circadian Regulation of Glutathione Levels and Biosynthesis in Drosophila melanogaster. PLoS ONE 7(11): e50454. https://doi.org/10.1371/journal.pone.0050454
Journal Title
Journal Volume
  • 7
Journal Issue/Number
  • 11
Academic Affiliation
Non-Academic Affiliation
权利声明
Funding Statement (additional comments about funding)
  • This research was supported by National Institutes of Health (NIH) R21: NIH R21 NS075500 to JMG and SNR, and in part by NIH R21AG038989 grant toJMG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Publisher
Peer Reviewed
Language
Replaces

关联

Parents:

This work has no parents.

属于 Collection:

单件

缩略图 标题 上传日期 公开度 行动
file details BeaverLauraMZoologyCircadianRegulationGlutathione.pdf 2017-07-17 公开 下载