Review
Cell Biology
Rebecca Charles, Philip Eaton
Summary: Cell responses to changes in redox state are mediated by reversible protein modifications, which can alter protein activities or interactions. These modifications are crucial for cells' homeostatic responses to environmental changes in redox state. The dysregulation of these redox regulatory mechanisms can contribute to pathophysiology. This review focuses on the redox control of soluble epoxide hydrolase (sEH), its different oxidative modifications, and their impact on cardiovascular physiology and disease progression during stress.
Article
Biochemistry & Molecular Biology
Yang Zhou, Xiang-Chong Wang, Jia-Hui Wei, Hong-Mei Xue, Wen-Tao Sun, Guo-Wei He, Qin Yang
Summary: This study revealed that both soluble epoxide hydrolase (sEH) and canonical transient receptor potential 3 (TRPC3) channels play a role in homocysteine-induced cardiac hypertrophy. Inhibition of sEH can alleviate pathological damage and improve cardiac function. In addition, sEH activation leads to upregulation of TRPC3 channels through an EETs-dependent manner.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Yasuhiro Kihara, Erina Nishimura, Chisato Kanai, Yoshikazu Kitano, Eriko Suzuki, Keiji Hasumi
Summary: Soluble epoxide hydrolase is an important enzyme involved in inflammation and metabolism regulation. The N-terminal phosphatase activity of the enzyme has been poorly understood due to the lack of selective inhibitors. This study identifies 4-aminobenzoic and 3-amino-4-hydroxy benzoic acid as selective competitive inhibitors for N-phos.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Matthieu Leuillier, Thomas Duflot, Severine Menoret, Hind Messaoudi, Zoubir Djerada, Deborah Groussard, Raphael G. P. Denis, Laurence Chevalier, Ahmed Karoui, Baptiste Panthu, Pierre-Alain Thiebaut, Isabelle Schmitz-Afonso, Severine Nobis, Cynthia Campart, Tiphaine Henry, Camille Sautreuil, Serge H. Luquet, Olivia Beseme, Catherine Feliu, Helene Peyret, Lionel Nicol, Jean-Paul Henry, Sylvanie Renet, Paul Mulder, Debin Wan, Laurent Tesson, Jean-Marie Heslan, Angeline Duche, Sebastien Jacques, Frederic Ziegler, Valery Brunel, Gilles J. P. Rautureau, Christelle Monteil, Jean-Luc do Rego, Jean-Claude do Rego, Carlos Afonso, Bruce Hammock, Anne-Marie Madec, Florence Pinet, Vincent Richard, Ignacio Anegon, Christophe Guignabert, Christophe Morisseau, Jeremy Bellien
Summary: The physiological role of the N-terminal phosphatase activity (sEH-P) of soluble epoxide hydrolase (sEH-H) was investigated using CRISPR/Cas9 to generate a knock-in (KI) rat line lacking sEH-P activity. The study found that sEH-P KI rats exhibited decreased metabolism of lysophosphatidic acids, decreased weight and fat mass gain, and increased insulin sensitivity. Moreover, sEH-P KI rats showed increased lipolysis and enhanced energy expenditure, which potentiated brown adipose thermogenesis. Additionally, sEH-P KI rats fed a high-fat diet did not experience weight gain, fat mass accumulation, insulin resistance, or hepatic steatosis, and they also exhibited enhanced cardiac mitochondrial activity and protection against ischemia-reperfusion injury. Overall, the findings highlight the importance of sEH-P in energy and fat metabolism and its potential therapeutic significance in the management of obesity and cardiac complications.
JOURNAL OF ADVANCED RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jang Hoon Kim, Yun-Chan Huh, Mok Hur, Woo Tae Park, Youn-Ho Moon, Tae Il Kim, Yong Il Kim, Seon Mi Kim, Jeonghoon Lee, Ik Soo Lee
Summary: A Glycyrrhiza uralensis extract showed potential inhibition of sEH, a target enzyme for treating inflammation and cardiovascular disease. Compounds 1-11 were isolated and tested, with compound 10 exhibiting the strongest inhibitory activity. Further evaluation in cells and animals is needed for compound 10.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Wen-Yu Zhao, Xin-Yue Zhang, Mei-Rong Zhou, Xiang-Ge Tian, Xia Lv, Hou-Li Zhang, Sa Deng, Bao-Jing Zhang, Cheng-Peng Sun, Xiao-Chi Ma
Summary: The inhibition of soluble epoxide hydrolase (sEH) is considered an effective treatment for inflammation-related diseases. Two novel sEH inhibitors were identified from Alisma orientate, providing potential leads for the development of sEH inhibitors based on protostane-type triterpenoids. In-depth studies revealed the mechanism of inhibition and highlighted the role of amino acid residue Ser374 in the activity of the inhibitors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Weimin Yu, Siqi Li, Haixia Wu, Pingping Hu, Lili Chen, Chunyu Zeng, Xiaoyong Tong
Summary: The study showed that inhibiting sEH can alleviate atherosclerosis caused by endothelial Nox4 dysfunction, potentially through suppression of ER stress. Endothelial Nox4 dysfunction can lead to inflammation, and inhibiting sEH and ER stress is beneficial for alleviating atherosclerosis.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Wen-Yu Zhao, Juan-Juan Yan, Min Zhang, Chao Wang, Lei Feng, Xia Lv, Xiao-Kui Huo, Cheng-Peng Sun, Li-Xia Chen, Xiao-Chi Ma
Summary: The study found that the extract of Inula britanica exhibited inhibitory effects against sEH, leading to the isolation of several new compounds with significant inhibitory effects. Molecular docking and dynamics analysis suggested that compounds 10 and 13 could be potential candidates for the development of sEH inhibitors.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Rebecca L. Charles, Giancarlo Abis, Beatriz F. Fernandez, Sebastian Guttzeit, Roberto Buccafusca, Maria R. Conte, Philip Eaton
Summary: The study revealed that H2O2 activates sEH by forming an intra-disulfide bond, increasing its catalytic efficiency. This oxidative activation mechanism also sensitizes sEH to inhibition by lipid electrophiles. The renin-angiotensin system regulates the intra-disulfide bond activation of sEH, leading to a decrease in EET/DHET ratio and an increase in blood pressure.
Article
Biochemistry & Molecular Biology
Nhien Nguyen, Christophe Morisseau, Dongyang Li, Jun Yang, Eileen Lam, D. Blake Woodside, Bruce D. Hammock, Pei-an Betty Shih
Summary: This study investigated the expression and activity of soluble epoxide hydrolase (sEH) in healthy women and women with anorexia nervosa. The results showed a correlation between sEH and body mass index, as well as a complex relationship with age and anxiety.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yun Ding, Svetlana Belyanskaya, Jennifer L. DeLorey, Jeffrey A. Messer, G. Joseph Franklin, Paolo A. Centrella, Barry A. Morgan, Matthew A. Clark, Steven R. Skinner, Jason W. Dodson, Peng Li, Joseph P. Marino, David I. Israel
Summary: The inhibition of soluble epoxide hydrolase (sEH) has emerged as a new approach to treat cardiovascular and respiratory diseases. Through structure-activity relationship studies, inhibitors based on 1,3,5-triazine chemotype have been discovered, leading to the identification of a clinical candidate for COPD.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Christian Grinan-Ferre, Julia Companys-Alemany, Julia Jarne-Ferrer, Sandra Codony, Celia Gonzalez-Castillo, Daniel Ortuno-Sahagun, Lluisa Vilageliu, Daniel Grinberg, Santiago Vazquez, Merce Pallas
Summary: The study demonstrated that the sEH inhibitor UB-EV-52 improved memory and spatial cognition in NPC mice, increased body weight and lifespan, reduced inflammatory gene expression, and decreased autophagic markers. Additionally, lipid profile analysis showed a significant reduction in lipid storage in the liver and some slight changes in the brain tissue of treated NPC mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Juan Zhang, Min Zhang, Xiao-Kui Huo, Jing Ning, Zhen-Long Yu, Christophe Morisseau, Cheng-Peng Sun, Bruce D. Hammock, Xiao-Chi Ma
Summary: Soluble epoxide hydrolase (sEH) plays a critical role in inflammation by modulating levels of epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids (EpFAs). Wedelolactone (WED), a small molecule, targets sEH, suppresses its activity, and enhances EET levels, attenuating inflammation and oxidative stress. In an LPS-stimulated ALI animal model, pharmacological sEH inhibition or sEH knockout alleviates pulmonary damage, suppresses macrophage activation, and reduces inflammation and oxidative stress.
ACS CENTRAL SCIENCE
(2023)
Article
Chemistry, Medicinal
Fangyu Du, Wenjiao Sun, Christophe Morisseau, Bruce D. Hammock, Xuefei Bao, Qiu Liu, Chao Wang, Tan Zhang, Hao Yang, Jun Zhou, Wei Xiao, Zhongbo Liu, Guoliang Chen
Summary: A new series of sEH inhibitors has been designed with improved binding properties and higher inhibition potency, among which compound B401 demonstrated potential therapeutic efficacy in sepsis. Molecular docking and in vitro studies supported the favorable activity of B401, highlighting its promise as a potential treatment for sepsis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Fangyu Du, Ruolin Cao, Lu Chen, Jianwen Sun, Yajie Shi, Yang Fu, Bruce D. Hammock, Zhonghui Zheng, Zhongbo Liu, Guoliang Chen
Summary: A new memantyl urea derivative, A20, was identified as a potent sEH inhibitor that can alleviate pain and improve the health status of rats, making it a promising candidate for the treatment of neuropathic pain.
ACTA PHARMACEUTICA SINICA B
(2022)