Publication Date:
2013-07-03
Description:
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 O2-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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969381/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969381/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Dengke K -- Rothe, Michael -- Zheng, Shu -- Bhatla, Nikhil -- Pender, Corinne L -- Menzel, Ralph -- Horvitz, H Robert -- GM24663/GM/NIGMS NIH HHS/ -- R01 GM024663/GM/NIGMS NIH HHS/ -- R37 GM024663/GM/NIGMS NIH HHS/ -- T32 GM007484/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 2;341(6145):554-8. doi: 10.1126/science.1235753. Epub 2013 Jun 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biology, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23811225" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Caenorhabditis elegans/genetics/*metabolism
;
Caenorhabditis elegans Proteins/*metabolism
;
Disease Models, Animal
;
Eicosanoids/metabolism
;
Evolution, Molecular
;
Fatty Acids, Unsaturated/metabolism
;
Hypoxia-Inducible Factor 1/*metabolism
;
Oxygen/*metabolism
;
Reperfusion Injury/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
