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

Purba, Endang R.; Leuhery, Elsa A.; Oguro, Ami; Imaoka, Shingi

doi:10.1016/j.dmpk.2014.09.002

Cited by 4 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that the discrepancy between our results and those of EnayetAllah et al may be due to differences in cell types and experimental conditions. Notably, the sEH Glu287Arg variant has lower PT activity and is associated with hyperlipidemia and calcification in CAD patients . As of today, the role of PT and EH activity of sEH on cholesterol metabolism has yet to be understood, so further investigations delineating the roles and molecular mechanism underlying the effect of EH and PT activity of sEH on cholesterol metabolism and atherosclerosis are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…36 Our current findings further con- PT activity and is associated with hyperlipidemia and calcification in CAD patients. [13][14][15] As of today, the role of PT and EH activity of sEH on cholesterol metabolism has yet to be understood, so further investigations delineating the roles and molecular mechanism underlying the effect of EH and PT activity of sEH on cholesterol metabolism and atherosclerosis are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple lines of evidence demonstrate that the PT domain of sEH also has a crucial role in the regulation of cholesterol metabolism and cell growth in hepatocytes . Moreover, the sEH Glu287Arg mutant, which has reduced PT activity, is known to be a risk factor for the development of coronary artery disease (CAD) . Additionally, this sEH polymorphism is closely associated with the increase in plasma cholesterol and triglyceride in familial hypercholesterolaemia patients .…”

Section: Introductionmentioning

confidence: 99%

“…11,12 Moreover, the sEH Glu287Arg mutant, which has reduced PT activity, is known to be a risk factor for the development of coronary artery disease (CAD). 13,14 Additionally, this sEH polymorphism is closely associated with the increase in plasma cholesterol and triglyceride in familial hypercholesterolaemia patients. 15 However, the role of the PT activity of sEH in the cholesterol metabolism of macrophage foam cells remains to be investigated.…”

mentioning

confidence: 97%

See 3 more Smart Citations

The phosphatase activity of soluble epoxide hydrolase regulates ATP‐binding cassette transporter‐A1‐dependent cholesterol efflux

Lien

Chen

Lee

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

The contribution of soluble epoxide hydrolase (sEH) to atherosclerosis has been well defined. However, less is understood about the role of sEH and its underlying mechanism in the cholesterol metabolism of macrophages. The expression of sEH protein was increased in atherosclerotic aortas of apolipoprotein E‐deficient mice, primarily in macrophage foam cells. Oxidized low‐density lipoprotein (oxLDL) increased sEH expression in macrophages. Genetic deletion of sEH (sEH−/−) in macrophages markedly exacerbated oxLDL‐induced lipid accumulation and decreased the expression of ATP‐binding cassette transporters‐A1 (ABCA1) and apolipoprotein AI‐dependent cholesterol efflux following oxLDL treatment. The down‐regulation of ABCA1 in sEH−/− macrophages was due to an increase in the turnover rate of ABCA1 protein but not in mRNA transcription. Inhibition of phosphatase activity, but not hydrolase activity, of sEH decreased ABCA1 expression and cholesterol efflux following oxLDL challenge, which resulted in increased cholesterol accumulation. Additionally, oxLDL increased the phosphatase activity, promoted the sEH‐ABCA1 complex formation and decreased the phosphorylated level of ABCA1 at threonine residues. Overexpression of phosphatase domain of sEH abrogated the oxLDL‐induced ABCA1 phosphorylation and further increased ABCA1 expression and cholesterol efflux, leading to the attenuation of oxLDL‐induced cholesterol accumulation. Our findings suggest that the phosphatase domain of sEH plays a crucial role in the cholesterol metabolism of macrophages.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 97%

See 2 more Smart Citations

The phosphatase activity of soluble epoxide hydrolase regulates ATP‐binding cassette transporter‐A1‐dependent cholesterol efflux

Lien

Chen

Lee

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…14 R103C and R287Q variants of sEH exhibited impaired phosphatase activity in vitro. 15 Despite these findings, the physiological role of sEH-P is far from being completely understood. A chemical probe, defined as “a selective small-molecule modulator of a protein’s function that allows the user to ask mechanistic and phenotypic questions about its molecular target in biochemical, cell-based or animal studies” 16 would be useful to investigate the physiological and pathophysiological roles of sEH-P.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Expression and HTS Assessment of Soluble Epoxide Hydrolase Phosphatase

et al. 2016

View full text Add to dashboard Cite

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that possesses an epoxide hydrolase and lipid phosphatase activity (sEH-P) at two distinct catalytic domains. While the physiological role of the epoxide hydrolase domain is well understood, the consequences of the phosphatase activity remain unclear. Herein we describe the bacterial expression of the recombinant N-terminal domain of sEH-P and the development of a high-throughput screening protocol using a sensitive and commercially available substrate fluorescein diphosphate. The usability of the assay system was demonstrated and novel inhibitors of sEH-P were identified

show abstract

CRISPR/Cas9-mediated inactivation of the phosphatase activity of soluble epoxide hydrolase prevents obesity and cardiac ischemic injury

Leuillier

Duflot

Ménoret

et al. 2023

Journal of Advanced Research

View full text Add to dashboard Cite

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

Cited by 4 publications

References 30 publications

The phosphatase activity of soluble epoxide hydrolase regulates ATP‐binding cassette transporter‐A1‐dependent cholesterol efflux

The phosphatase activity of soluble epoxide hydrolase regulates ATP‐binding cassette transporter‐A1‐dependent cholesterol efflux

Bacterial Expression and HTS Assessment of Soluble Epoxide Hydrolase Phosphatase

CRISPR/Cas9-mediated inactivation of the phosphatase activity of soluble epoxide hydrolase prevents obesity and cardiac ischemic injury

Contact Info

Product

Resources

About