Cytochrome P450 Drives a HIF-Regulated Behavioral Response to Reoxygenation by C. elegans
Author(s)Ma, Dengke; Zheng, Shu; Bhatla, Nikhil; Pender, Corinne Lenore; Horvitz, H. Robert; Rothe, Michael; Menzel, Ralph; ... Show more Show less
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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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; McGovern Institute for Brain Research at MIT
American Association for the Advancement of Science (AAAS)
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.
Author's final manuscript