ArticleThe Journal of biological chemistry2008
Opposite regulation of cholesterol levels by the phosphatase and hydrolase domains of soluble epoxide hydrolase.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 63 citations in OpenAlex.
- Mice deficient in the phosphatase activity of sEH show decreased levels of the endocannabinoid 2-AG in the olfactory bulb and depressive-like behavior.FEBS letters · 2024Article
- The involvement of soluble epoxide hydrolase in the development of cardiovascular diseases through epoxyeicosatrienoic acids.Frontiers in pharmacology · 2024Review
- CRISPR/Cas9-mediated inactivation of the phosphatase activity of soluble epoxide hydrolase prevents obesity and cardiac ischemic injury.Journal of advanced research · 2023Article
- Multitarget molecule, PTUPB, to treat diabetic nephropathy in rats.British journal of pharmacology · 2021Article
- Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson's Disease: A New Therapeutic Strategy.Biomolecules · 2020Review
- The phosphatase activity of soluble epoxide hydrolase regulates ATP-binding cassette transporter-A1-dependent cholesterol efflux.Journal of cellular and molecular medicine · 2019Article
- N-Substituted amino acid inhibitors of the phosphatase domain of the soluble epoxide hydrolase.Biochemical and biophysical research communications · 2019Article
- Soluble Epoxide Hydrolase and Brain Cholesterol Metabolism.Frontiers in molecular neuroscience · 2019Review
- Estrogen-dependent epigenetic regulation of soluble epoxide hydrolase via DNA methylation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The Role of Cytochrome P450 Epoxygenases, Soluble Epoxide Hydrolase, and Epoxyeicosatrienoic Acids in Metabolic Diseases.Advances in nutrition (Bethesda, Md.) · 2016Review
- A dual COX-2/sEH inhibitor improves the metabolic profile and reduces kidney injury in Zucker diabetic fatty rat.Prostaglandins & other lipid mediators · 2016Article
- Serglycin protects against high fat diet-induced increase in serum LDL in mice.Glycoconjugate journal · 2015Article
- Role of phosphatase activity of soluble epoxide hydrolase in regulating simvastatin-activated endothelial nitric oxide synthase.Scientific reports · 2015Article
- Arachidonic acid monooxygenase: Genetic and biochemical approaches to physiological/pathophysiological relevance.Prostaglandins & other lipid mediators · 2015Review
- The 2014 Bernard B. Brodie award lecture-epoxide hydrolases: drug metabolism to therapeutics for chronic pain.Drug metabolism and disposition: the biological fate of chemicals · 2015Review
- The cytochrome P450 epoxygenase pathway regulates the hepatic inflammatory response in fatty liver disease.PloS one · 2014Article
- Opposite effects of gene deficiency and pharmacological inhibition of soluble epoxide hydrolase on cardiac fibrosis.PloS one · 2014Article
- Development of an HTS assay for EPHX2 phosphatase activity and screening of nontargeted libraries.Analytical biochemistry · 2013Article
- Role of soluble epoxide hydrolase phosphatase activity in the metabolism of lysophosphatidic acids.Biochemical and biophysical research communications · 2012Article
- Lysophosphatidic acids are new substrates for the phosphatase domain of soluble epoxide hydrolase.Journal of lipid research · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with two catalytic domains: a C-terminal epoxide hydrolase domain and an N-terminal phosphatase domain. Epidemiology and animal studies have attributed a variety of cardiovascular and anti-inflammatory effects to the C-terminal epoxide hydrolase domain. The recent association of sEH with cholesterol-related disorders, peroxisome proliferator-activated receptor activity, and the isoprenoid/cholesterol biosynthesis pathway additionally suggest a role of sEH in regulating cholesterol metabolism. Here we used sEH knock-out (sEH-KO) mice and transfected HepG2 cells to evaluate the phosphatase and hydrolase domains in regulating cholesterol levels. In sEH-KO male mice we found a approximately 25% decrease in plasma total cholesterol as compared with wild type (sEH-WT) male mice. Consistent with plasma cholesterol levels, liver expression of HMG-CoA reductase was found to be approximately 2-fold lower in sEH-KO male mice. Additionally, HepG2 cells stably expressing human sEH with phosphatase only or hydrolase only activity demonstrate independent and opposite roles of the two sEH domains. Whereas the phosphatase domain elevated cholesterol levels, the hydrolase domain lowered cholesterol levels. Hydrolase inhibitor treatment in sEH-WT male and female mice as well as HepG2 cells expressing human sEH resulted in higher cholesterol levels, thus mimicking the effect of expressing the phosphatase domain in HepG2 cells. In conclusion, we show that sEH regulates cholesterol levels in vivo and in vitro, and we propose the phosphatase domain as a potential therapeutic target in hypercholesterolemia-related disorders.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.