Cytochrome P450 Drives a HIF-Regulated Behavioral Response to Reoxygenation by C. elegans
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Author(s)
Ma, Dengke
Zheng, Shu
Bhatla, Nikhil
Pender, Corinne Lenore
Rothe, Michael
Menzel, Ralph
Horvitz, Howard Robert
Date Issued
June 2013
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Ma, D. K., M. Rothe, S. Zheng, N. Bhatla, C. L. Pender, R. Menzel, and H. R. Horvitz. “Cytochrome P450 Drives a HIF-Regulated Behavioral Response to Reoxygenation by C. Elegans.” Science 341, no. 6145 (August 2, 2013): 554–558.
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Author's final manuscript
Abstract
Oxygen deprivation followed by reoxygenation causes pathological responses in many disorders, including ischemic stroke, heart attacks, and reperfusion injury. Key aspects of ischemia-reperfusion can be modeled by a Caenorhabditis elegans behavior, the O2-ON response, which is suppressed by hypoxic preconditioning or inactivation of the O[subscript 2]-sensing HIF (hypoxia-inducible factor) hydroxylase EGL-9. From a genetic screen, we found that the cytochrome P450 oxygenase CYP-13A12 acts in response to the EGL-9–HIF-1 pathway to facilitate the O2-ON response. CYP-13A12 promotes oxidation of polyunsaturated fatty acids into eicosanoids, signaling molecules that can strongly affect inflammatory pain and ischemia-reperfusion injury responses in mammals. We propose that roles of the EGL-9–HIF-1 pathway and cytochrome P450 in controlling responses to reoxygenation after anoxia are evolutionarily conserved.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1126/science.1235753
