The metabolism of lysophosphatidic acids by allelic variants of human soluble epoxide hydrolase

Drug Metabolism and Pharmacokinetics
Endang R PurbaSusumu Imaoka

Abstract

Lysophosphatidic acids (LPAs) are phospholipids which have many physiological and pathophysiological functions. The human soluble epoxide hydrolase (sEH) plays a role in the metabolism of xenobiotics through its metabolism of aromatic hydrocarbon epoxides such as styrene oxide. sEH also has a phosphatase activity, and metabolizes LPAs. In this study, we investigated a purified wild-type (WT) and six allelic variants of sEH to evaluate differences in their activities toward LPAs. We found that the R103C and R287Q showed significantly lower activity than the WT sEH. We also found that the R103C and R287Q had significantly lower activity even when applied to only the N-terminal or C-terminal domain. The kinetic study determined that the R103C and R287Q had a lower Vmax/Km ratio toward stearoyl-LPA than the other variants. In a previous study, we found that WT sEH suppressed vascular endothelial growth factor (VEGF) mRNA in Hep3B cells; in the present experiments, all sEH variants except V442A suppressed VEGF mRNA levels in Hep3B cells. These results suggest that the R103C and R287Q have lower phosphatase activity, but that all the allelic variants have similar effects on VEGF suppression.

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Citations

Mar 25, 2016·Journal of Biomolecular Screening·Franca-Maria KlinglerEwgenij Proschak
Aug 23, 2019·Journal of Cellular and Molecular Medicine·Chih-Chan LienTzong-Shyuan Lee

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