Cytochrome P450 Drives a HIF-Regulated Behavioral Response to Reoxygenation by C. elegans

Abstract

As the Worm Squirms Restoration of oxygen supply to cells that have been deprived of oxygen actually causes further damage to cells and tissues. Such responses, known as reperfusion injury, contribute to the deadly effects of heart attacks and strokes in humans. Lack of oxygen is sensed directly by a prolyl hydroxylase known as EGL-9 in worms and EGLN2 in mammals. Inhibition of EGL-9 can reduce damage caused by reperfusion of tissues with oxygen, but how such beneficial effects are mediated is not clear. Ma et al. (p. 554 , published online 27 June) used a genetic screen in the nematode Caenorhabditis elegans , which has a behavioral response to reoxygenation in which the animals increase their movement, to find factors that interact with EGL-9. They identified the cytochrome p450 oxygenase CYP-13A12 as such a factor. Some cytochrome p450 enzymes act on polyunsaturated fatty acids to make cellular signaling molecules known as eicosanoids. The effects of CYP-13A23 were mediated by eicosanoids. Because the regulatory pathways involved appear to be evolutionarily conserved, the results may aid understanding and management of reperfusion injury in humans.