title: Peroxisomal translocation of soluble epoxide hydrolase protects against ischemic stroke injury.
abstract: Soluble epoxide hydrolase (sEH) contributes to cardiovascular disease, including stroke, although the exact mechanism remains unclear. While primarily a cytosolic enzyme, sEH can translocate into peroxisomes. The relevance of this for stroke injury is not understood. We tested the hypothesis that sEH-mediated injury is tied to the cytoplasmic localization. We found that a human sEH variant possessing increased affinity to peroxisomes reduced stroke injury in sEH-null mice, whereas infarcts were significantly larger when peroxisomal translocation of sEH was disrupted. We conclude that sEH contributes to stroke injury only when localized in the cytoplasm, while peroxisomal sEH may be protective.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA.|Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Nelson
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Wenri
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Nabil J
authors.initials: NJ
authors.lastname: Alkayed
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Ines P
authors.initials: IP
authors.lastname: Koerner
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003600:Cytosol / Q000201:enzymology* / Q000473:pathology; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D020675:Peroxisomes / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D021381:Protein Transport; D020521:Stroke / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D004851:Epoxide Hydrolases