Abstract:
Circadian clocks are internal mechanisms regulating many physiological processes.
Research suggests that the circadian clock may regulate repair of cellular damage caused
by reactive oxygen species (ROS), but molecular pathways from the clock to ROS repair
are not known. The gene cncC, known in mammals as Nrf2, and its repressor keap1,
mediate the cellular responses to oxidative stress and activate genes such as glutathiones-
transferase (gstD1) and glutamate cysteine ligase (Gclc), which encode important
detoxification enzymes. The question addressed in this study was whether clock genes
regulate the response to oxidative stress in Drosophila melanogaster by stimulating
expression of cncC/Nrf2 and keap1, which then activate gstD1 and Gclc. Expression
profiles of cncC/Nrf2, keap1, gstD1, and Gclc were measured in flies with normal or
disrupted clocks over a 24 h period. We show the circadian clock does not control
transcription of cncC/Nrf2 and keap1. In contrast, the effector genes gstD1 and Gclc
showed daily rhythms of expression, which were disrupted in clock mutants. These
results suggest that the clock may modulate the expression of genes involved in ROS
protection. This study provides new knowledge on ROS regulation, which is a rising
health concern due to the cellular damage they cause.
