Oxidative Stress Response Genes: A Circadian Connection?

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