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: Jonathan W Nelson, Wenri Zhang, Nabil J Alkayed, Ines P Koerner
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 35 Issue 9 Pg. 1416-20 (Sep 2015) ISSN: 1559-7016 [Electronic] United States
• PMID: 26126869 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epoxide Hydrolases

Topics

• Animals
• Brain Ischemia (enzymology, genetics, pathology)
• Cytosol (enzymology, pathology)
• Epoxide Hydrolases (genetics, metabolism)
• Humans
• Mice
• Mice, Mutant Strains
• Peroxisomes (enzymology, genetics, pathology)
• Protein Transport
• Stroke (enzymology, genetics, pathology)