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Prostaglandins & Other Lipid Mediators

Weicang Wang, Jun Yang, Haixia Yang, Katherine Z Sanidad, Bruce D Hammock, Daeyoung Kim, Guodong Zhang
Obesity is a serious health problem in the US and is associated with increased risks of various human diseases. To date, the mechanisms by which obesity increases the risks of a wide range of human diseases are not well understood. Here we used a LC-MS/MS-based lipidomics, which can analyze >100 bioactive lipid mediators produced by cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes, to analyze plasma profiles of lipid mediators in high-fat diet induced obesity in C57BL/6 mice. Our results show that the plasma concentrations of epoxyoctadecenoic acids (EpOMEs, also termed as leukotoxins) are significantly increased in plasma of high-fat diet-fed mice, in addition, EpOMEs are among the most abundant lipid mediators detected in mouse plasma...
November 30, 2016: Prostaglandins & Other Lipid Mediators
J Rafael Montenegro-Burke, Jessica A Sutton, Lisa M Rogers, Ginger L Milne, John A McLean, David M Aronoff
The highly orchestrated transcriptional and metabolic reprogramming during activation drastically transforms the main functions and physiology of human macrophages across the polarization spectrum. Lipids, for example, can modify protein function by acting remotely as signaling molecules but also locally by altering the physical properties of cellular membranes. These changes play key roles in the functions of highly plastic immune cells due to their involvement in inflammation, immune responses, phagocytosis and wound healing processes...
November 15, 2016: Prostaglandins & Other Lipid Mediators
Elizabeth Berry, Yanzhou Liu, Li Chen, Austin M Guo
Eicosanoids are bioactive lipid products primarily derived from the oxidation of arachidonic acid (AA). The individual contributions of eicosanoids and stem cells to wound healing have been of great interest. This review focuses on how stem cells work in concert with eicosanoids to create a beneficial environment in the wound bed and in the promotion of wound healing. Stem cells contribute to wound healing through modulating inflammation, differentiating into skin cells or endothelial cells, and exerting paracrine effects by releasing various potent growth factors...
November 5, 2016: Prostaglandins & Other Lipid Mediators
Xuehong Liu, Zu-Yuan Qian, Fuchun Xie, Wei Fan, Jonathan W Nelson, Xiangshu Xiao, Sanjiv Kaul, Anthony P Barnes, Nabil J Alkayed
Epoxyeicosatrienoic acids (EETs) are potent vasodilators that play important roles in cardiovascular physiology and disease, yet the molecular mechanisms underlying the biological actions of EETs are not fully understood. Multiple lines of evidence suggest that the actions of EETs are in part mediated via G protein-coupled receptor (GPCR) signaling, but the identity of such a receptor has remained elusive. We sought to identify 14,15-EET-responsive GPCRs. A set of 105 clones were expressed in Xenopus oocyte and screened for their ability to activate cAMP-dependent chloride current...
September 17, 2016: Prostaglandins & Other Lipid Mediators
Cristine Kolling Konopka, Verônica Farina Azzolin, Francine Carla Cadoná, Alencar Kolinski Machado, Eduardo Bortoluzzi Dornelles, Fernanda Barbisan, Ivana Beatrice Mânica da Cruz
Misoprostol, prostaglandin E1 analogue, used for labour induction. However, one-third of patients who have labour induced with prostaglandins do not reach vaginal delivery. The differential expression of prostaglandin receptors in myometrial cells could account for this differential response. Since delivery physiology also involves modulation of oxidative metabolism that can be potentially affected by pharmacological drugs, in the present investigation the role of misoprostol on expression of prostaglandin receptors, and oxidative markers of myometrial cells was evaluated...
September 16, 2016: Prostaglandins & Other Lipid Mediators
Jan Matczuk, Anna Zalewska, Bartłomiej Łukaszuk, Marta Garbowska, Adrian Chabowski, Małgorzata Żendzian-Piotrowska, Krzysztof Kurek
BACKGROUND: Diabetes is one of the most common metabolic diseases. Moreover, previous studies indicate that diabetes may cause changes in the salivary glands phenotype and in the composition of saliva itself. Therefore, the main objective of this study was to determine the effects of streptozotocin induced diabetes on lipid profile of the rat salivary glands. METHODS: Male Wistar rats were divided into two groups: control and STZ-induced diabetes. At the end of the experiment all animals were sacrificed and samples of the parotid and submandibular salivary glands were excised...
September 14, 2016: Prostaglandins & Other Lipid Mediators
John R Montford, Allison M B Lehman, Micah S Scobey, Mary C M Weiser-Evans, Raphael A Nemenoff, Seth B Furgeson
The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme controls the release of arachidonic acid from membrane bound phospholipids and is the rate-limiting step in production of eicosanoids. A variety of different kidney injuries activate cPLA2α, therefore we hypothesized that cPLA2α activity would regulate pathologic processes in HK-2 cells, a human renal tubular epithelial cell line, by regulating cell phenotype and proliferation. In two lentiviral cPLA2α-silenced knockdowns, we observed decreased proliferation and increased apoptosis compared to control HK-2 cells...
November 2016: Prostaglandins & Other Lipid Mediators
Mohamed M Katary, Chelsey Pye, Ahmed A Elmarakby
The pro-inflammatory cyclooxygenase (COX)-derived prostaglandins and the anti-inflammatory cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of renal injury. The current study examined whether COX inhibition augments the reno-protective effects of increased EETs levels via inhibiting EETs degradation by soluble epoxide hydrolase (sEH) in diabetic rats. Streptozotocin (50mg/kg, i.v) was used to induce diabetes in male Sprague Dawley rats. Rats were then divided into 5 groups (n=6-8); control non diabetic, diabetic, diabetic treated with the sEH inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), diabetic treated with the COX inhibitor meloxicam and diabetic treated with meloxicam plus t-AUCB for 2 months...
September 2, 2016: Prostaglandins & Other Lipid Mediators
Juan A Giménez-Bastida, Takashi Suzuki, Katie C Sprinkel, William E Boeglin, Claus Schneider
The hemiketal (HK) eicosanoids HKE2 and HKD2 are the major products resulting from the biosynthetic cross-over of the 5-lipoxygenase and cyclooxygenase-2 pathways. They are formed by activated human leukocytes ex vivo, and, therefore, may be involved in regulation of the inflammatory response as autocrine or paracrine mediators. HKE2 and HKD2 are not commercially available and, so far, no method for their total chemical synthesis has been reported. The limited availability has impeded the characterization of their biological effects...
September 2, 2016: Prostaglandins & Other Lipid Mediators
Nader G Abraham
No abstract text is available yet for this article.
September 2016: Prostaglandins & Other Lipid Mediators
Subreen A Khatib, Emily L Rossi, Laura W Bowers, Stephen D Hursting
Today's world population has an unprecedented risk of dying from the consequences of being overweight and obese. Chronic diseases such as cardiovascular disease, type 2 diabetes, and cancer are often accelerated because of excessive adiposity. Various biological mechanisms are implicated in the obesity-cancer link, particularly local and systemic inflammation as well as altered growth factor signaling pathways. In order to combat obesity-induced inflammation and the resulting increases in cancer risk and progression, the identification of safe and effective mechanism-based interventions is imperative...
September 2016: Prostaglandins & Other Lipid Mediators
James M Luther, Nancy J Brown
Epoxyeicosatrienoic acids (EETs) are formed from arachidonic acid by the action of P450 epoxygenases (CYP2C and CYP2J). Effects of EETs are limited by hydrolysis by soluble epoxide hydrolase to less active dihydroxyeicosatrienoic acids. Studies in rodent models provide compelling evidence that epoxyeicosatrienoic acids exert favorable effects on glucose homeostasis, either by enhancing pancreatic islet cell function or by increasing insulin sensitivity in peripheral tissues. Specifically, the tissue expression of soluble epoxide hydrolase appears to be increased in rodent models of obesity and diabetes...
September 2016: Prostaglandins & Other Lipid Mediators
Md Abdul Hye Khan, Sung Hee Hwang, Amit Sharma, John A Corbett, Bruce D Hammock, John D Imig
Cyclooxygenase (COX) and soluble epoxide hydrolase (sEH) inhibitors have therapeutic potential. The present study investigated efficacy of a novel dual acting COX-2/sEH inhibitor, PTUPB in type 2 diabetic Zucker Diabetic Fatty (ZDF) rats. Male ZDF rats were treated with vehicle or PTUPB (10mg/kg/d, i.p.) for 8 weeks. At the end of the 8-week experimental period, ZDF rats were diabetic (fasting blood glucose, 287±45mg/dL) compared to Zucker Diabetic Lean rats (ZDL, 99±6mg/dL), and PTUPB treatment improved glycemic status in ZDF rats (146±6mg/dL)...
September 2016: Prostaglandins & Other Lipid Mediators
Harold E Bays, Christie M Ballantyne, Ralph T Doyle, Rebecca A Juliano, Sephy Philip
Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved at a dose of 4g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500mg/dL) hypertriglyceridemia. This post-hoc exploratory analysis examined the relationship of icosapent ethyl dose with EPA concentrations in plasma and red blood cells (RBCs) across 3 clinical studies-a phase 1 pharmacokinetic study in healthy adult volunteers and 2 pivotal phase 3 studies (MARINE and ANCHOR) in adult patients with hypertriglyceridemia-and examined the relationship between EPA levels and TG-lowering effects in MARINE and ANCHOR...
September 2016: Prostaglandins & Other Lipid Mediators
Shailendra P Singh, Joseph Schragenheim, Jian Cao, John R Falck, Nader G Abraham, Lars Bellner
BACKGROUND/OBJECTIVES: Obesity is a risk factor in the development of type 2 diabetes mellitus (DM2), which is associated with increased morbidity and mortality, predominantly as a result of cardiovascular complications. Increased adiposity is a systemic condition characterized by increased oxidative stress (ROS), increased inflammation, inhibition of anti-oxidant genes such as HO-1 and increased degradation of epoxyeicosatrienoic acids (EETs). We previously demonstrated that EETs attenuate mitochondrial ROS...
September 2016: Prostaglandins & Other Lipid Mediators
Michael A Wells, Kimberly C Vendrov, Matthew L Edin, Brian C Ferslew, Weibin Zha, Bobbie K H Nguyen, Rachel J Church, Fred B Lih, Laura M DeGraff, Kim L R Brouwer, A Sidney Barritt, Darryl C Zeldin, Craig R Lee
Non-alcoholic steatohepatitis (NASH) is an emerging public health problem without effective therapies. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into bioactive epoxyeicosatrienoic acids (EETs), which have potent anti-inflammatory and protective effects. However, the functional relevance of the CYP epoxyeicosanoid metabolism pathway in the pathogenesis of NASH remains poorly understood. Our studies demonstrate that both mice with methionine-choline deficient (MCD) diet-induced NASH and humans with biopsy-confirmed NASH exhibited significantly higher free EET concentrations compared to healthy controls...
September 2016: Prostaglandins & Other Lipid Mediators
David Sacerdoti, Paola Pesce, Marco Di Pascoli, Massimo Bolognesi
Epoxygenase-dependent metabolites of arachidonc acid, EETs and the heme-oxygenase (HO)-1/carbon monoxide/bilverdin system share similarities in their activity and mediators. They control endothelial function, dilating small arterial vessels, decrease blood pressure, protect the heart from ischemic and hypertensive cardiopathy, control renal circulation and function, promote angiogenesis and organ regeneration, oppose oxidative stress and inflammation, improve diabetes and obesity, have protective effects on the liver, and participate in portal hypertension...
September 2016: Prostaglandins & Other Lipid Mediators
Shaan S Naughton, Michael L Mathai, Deanne H Hryciw, Andrew J McAinch
The modern Western diet has been consumed in developed English speaking countries for the last 50 years, and is now gradually being adopted in Eastern and developing countries. These nutrition transitions are typified by an increased intake of high linoleic acid (LA) plant oils, due to their abundance and low price, resulting in an increase in the PUFA n-6:n-3 ratio. This increase in LA above what is estimated to be required is hypothesised to be implicated in the increased rates of obesity and other associated non-communicable diseases which occur following a transition to a modern Westernised diet...
September 2016: Prostaglandins & Other Lipid Mediators
Maayan Waldman, Stephen J Peterson, Michael Arad, Edith Hochhauser
Arachidonic acid (AA) is metabolized in mammals by enzymes of the CYP4A and 4F families to 20-hydroxyeicosatetraeonic acid (20-HETE) which plays an important role in the regulation of renal function, vascular tone and arterial pressure. In the vasculature, 20-HETE is a potent vasoconstrictor, the up-regulation of which contributes to inflammation, oxidative stress, endothelial dysfunction and an increase in peripheral vascular resistance in models of obesity, diabetes, ischemia/reperfusion, and vascular oxidative stress...
September 2016: Prostaglandins & Other Lipid Mediators
Hui Huang, Jing Weng, Mong-Heng Wang
Despite the optimization of blood glucose control and the therapeutic management of risk factors, obesity- and diabetes-induced cardiovascular diseases are still major health problems in the United States. Arachidonic acid (AA), an endogenous 20-carbon polyunsaturated fatty acid, is metabolized by cytochrome P450 (CYP) epoxygenases into epoxyeicosatrienoic acids (EETs), which are important lipid mediators with many beneficial effects in type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and obesity- and diabetes-induced cardiovascular diseases...
September 2016: Prostaglandins & Other Lipid Mediators
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