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https://www.readbyqxmd.com/read/28533326/prostaglandin-e-receptor-subtype-4-regulates-lipid-droplet-size-and-mitochondrial-activity-in-murine-subcutaneous-white-adipose-tissue
#1
Fan Ying, Yin Cai, Yu Cai, Yu Wang, Eva Hoi Ching Tang
The purpose of this study was to investigate whether genetic ablation of prostaglandin E receptor subtype 4 (EP4) affects white adipose tissue (WAT) remodeling mediated by β3-adrenergic stimulation. The selective β3-adrenergic agonist, CL316243 (1 mg/kg/d, i.p.) caused a greater increase in metabolic rate in EP4-knockout mice. CL316243 fragmented the unilocular lipid droplet into multilocular lipid vacuoles and increased mitochondrial biogenesis and its activity. These changes were amplified in mice with EP4 deficiency and were selectively seen in subcutaneous WAT...
May 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28465762/paricalcitol-pretreatment-attenuates-renal-ischemia-reperfusion-injury-via-prostaglandin-e2-receptor-ep4-pathway
#2
Yu Ah Hong, Keum Jin Yang, So Young Jung, Ki Cheol Park, Hyunsu Choi, Jeong Min Oh, Sang Ju Lee, Yoon Kyung Chang, Cheol Whee Park, Chul Woo Yang, Suk Young Kim, Hyeon Seok Hwang
The protective mechanism of paricalcitol remains unclear in renal ischemia-reperfusion (IR) injury. We investigated the renoprotective effects of paricalcitol in IR injury through the prostaglandin E2 (PGE2) receptor EP4. Paricalcitol was injected into IR-exposed HK-2 cells and mice subjected to bilateral kidney ischemia for 23 min and reperfusion for 24 hr. Paricalcitol prevented IR-induced cell death and EP4 antagonist cotreatment offset these protective effects. Paricalcitol increased phosphorylation of Akt and cyclic AMP responsive element binding protein (CREB) and suppressed nuclear factor-κB (NF-κB) in IR-exposed cells and cotreatment of EP4 antagonist or EP4 small interfering RNA blunted these signals...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28460684/effects-of-lpa2r-lpa3r-or-ep4r-agonists-on-luteal-or-endometrial-function-in%C3%A2-vivo-or-in%C3%A2-vitro-and-sirtuin-or-ep1r-ep2r-ep3r-or-ep4r-agonists-on-endometrial-secretion-of-pge-and-pgf2%C3%AE-in%C3%A2-vitro
#3
Magen E LaPorte, Yoshie S Weems, Alejandro Arreguin-Arevalo, Terry M Nett, Nicole Tsutahara, Tracy Sy, Jade Haberman, Michel Chon, Ronald D Randel, Charles W Weems
In previous work, an EP2 prostanoid receptor (EP2R) agonist in vivo increased mRNA expression of luteal LH receptors (LHR), unoccupied and occupied luteal; LHR, and circulating progesterone, while an EP3R or FPR agonist decreased; mRNA expression of luteal LHR, unoccupied and occupied luteal LHR, and; circulating progesterone. An EP4R and lysophosphatidic acid (LPA) LPA2R and LPA3R agonists were reported to inhibit luteal function and sirtuins have been proposed to increase prostaglandin synthesis. The objectives were to determine; whether an EP4R, LPA2R, or LPA3R agonist affect ovine luteal function in vivo or; in vitro...
June 2017: Theriogenology
https://www.readbyqxmd.com/read/28459136/pharmacokinetics-of-grapiprant-a-selective-ep4-prostaglandin-pge2-receptor-antagonist-after-2-mg-kg-oral-and-i-v-administrations-in-cats
#4
B Lebkowska-Wieruszewska, V De Vito, H Owen, A Poapholatep, M Giorgi
Drugs that provide effective analgesia in cats are limited. The aim of the study was to assess the pharmacokinetics of grapiprant after 2 mg/kg administration via p.o. and i.v. routes in cats. Six healthy adult cats were used according to an open, single-dose, two-treatment, two-period, randomized cross-over design. Cats were assigned to two treatment groups and administered with 2 mg/kg of grapiprant (pure powder) through p.o. and i.v. administration. Blood samples were collected at preassigned times and analysed by a validated HPLC method...
April 29, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28444901/pge2-receptor-subtype-1-ep1-regulates-mesenchymal-stromal-cell-osteogenic-differentiation-by-modulating-cellular-energy-metabolism
#5
M Feigenson, R A Eliseev, J H Jonason, B N Mills, R J O'Keefe
Mesenchymal stromal cells (MSCs) are multipotent progenitors capable of differentiation into osteoblasts and can potentially serve as a source for cell-based therapies for bone repair. Many factors have been shown to regulate MSC differentiation into the osteogenic lineage such as the Cyclooxygenase-2 (COX2)/Prostaglandin E2 (PGE2) signaling pathway that is critical for bone repair. PGE2 binds four different receptors EP1-4. While most studies focus on the role PGE2 receptors EP2 and EP4 in MSC differentiation, our study focuses on the less studied, receptor subtype 1 (EP1) in MSC function...
April 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28440186/the-double-roles-of-the-prostaglandin-e2-ep2-receptor-in-intracerebral-hemorrhage
#6
Xu Luo, Qiquan Zhu, Jie Zhang, Qin Huang, Zongyi Xie, Yuan Cheng
Intracerebral hemorrhage (ICH), a subtype of stroke, brings high morbidity and mortality to human beings. Multiple studies indicate that neuroinflammation, excitotoxicity, oxidative stress, cytotoxicity resulted from the degradation products of blood clot play vital roles in ICH-induced secondary brain injury, which contributes to deterioration of neurological outcome. Prostaglandin E2 (PGE2), a type of prostanoids commonly up-regulated in these progresses, is known to modulate numerous cellular and molecular processes and involve in various diseases, including ICH, cerebral ischemic, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) etc...
April 24, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28438981/acute-inflammation-reveals-gabaa-receptor-mediated-nociception-in-mouse-dorsal-root-ganglion-neurons-via-pge2-receptor-4-signaling
#7
In Jeong Jang, Alexander J Davies, Nozomi Akimoto, Seung Keun Back, Pa Reum Lee, Heung Sik Na, Hidemasa Furue, Sung Jun Jung, Yong Ho Kim, Seog Bae Oh
Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) primary afferent neurons through activation of Cl(-) permeable GABAA receptors but the physiologic role of GABAA receptors in the peripheral terminals of DRG neurons remains unclear. In this study, we investigated the role of peripheral GABAA receptors in nociception using a mouse model of acute inflammation. In vivo, peripheral administration of the selective GABAA receptor agonist muscimol evoked spontaneous licking behavior, as well as spinal wide dynamic range (WDR) neuron firing, after pre-conditioning with formalin but had no effect in saline-treated mice...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28432343/cox-1-pge2-ep4-alleviates-mucosal-injury-by-upregulating-%C3%AE-arr1-mediated-akt-signaling-in-colitis
#8
Xiaojie Peng, Jianzhong Li, Siwei Tan, Minyi Xu, Jin Tao, Jie Jiang, Huiling Liu, Bin Wu
COX-1/PGE2 is an important protective mediator in ulcerative colitis (UC). β-arrestin1 (β-arr1), which acts as a scaffold protein, is involved in PGE2-mediated signaling pathways. However, the interaction between PGE2 and β-arr1 in maintaining mucosal barrier integrity remains unexplored. In this study, we demonstrated that COX-1 and PGE2 were significantly decreased, and EP4 mRNA was downregulated in both UC patients and mice during the injury phase. PGE2 treatment was found to alleviate mucosal injury and induce EP4 expression during dextran sulfate sodium (DSS)-induced colitis in wild-type (WT) mice...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428256/regulation-of-lung-endothelial-permeability-and-inflammatory-responses-by-prostaglandin-a2-role-of-ep4-receptor
#9
Tomomi Ohmura, Yufeng Tian, Nicolene Sarich, Yunbo Ke, Angelo Meliton, Alok S Shah, Katrin Andreasson, Konstantin G Birukov, Anna A Birukova
A role of prostaglandin A2 (PGA2) in modulation of vascular endothelial function remains unknown. We investigated effects of PGA2 on pulmonary endothelial cell (EC) permeability and inflammatory activation and identified a receptor mediating these effects. PGA2 enhanced the EC barrier and protected against barrier dysfunction caused by vasoactive peptide thrombin and proinflammatory bacterial wall lipopolysacharide (LPS). Receptor screening using pharmacologic and molecular inhibitory approaches identified EP4 as a novel PGA2 receptor...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28425078/involvement-of-interstitial-cells-of-cajal-in-bladder-dysfunction-in-mice-with-experimental-autoimmune-encephalomyelitis
#10
Zhibo Jin, Yinghui Ding, Rui Xue, Zhankui Jia, Zhenlin Huang, Yafei Ding, Chaohui Gu, Jinjian Yang
BACKGROUND: Bladder dysfunction is an important symptom of experimental autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4 (EP4) in the bladder was accompanied by bladder dysfunction. Although many other studies have evaluated the lower urinary tract symptoms in multiple sclerosis, the mechanism remains unclear. OBJECTIVES: To investigate the effects of interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic bladder model induced by experimental autoimmune encephalomyelitis...
April 19, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28424169/identification-of-the-fatty-acid-activation-site-on-human-clc-2
#11
John Cuppoletti, Kirti P Tewari, Jayati Chakrabarti, Danuta H Malinowska
Fatty acids (including lubiprostone and cobiprostone) are human ClC-2 (hClC-2) Cl(-) channel activators. Molecular and cellular mechanisms underlying this activation were examined. Role of a 4-amino acid PKA activation site, RGET691 of hClC-2 was investigated using WT and mutant (AGET, RGEA and AGAA) hClC-2 expressed in 293EBNA cells as well as involvement of PKA, [cAMP]i, EP2 or EP4 receptor agonist activity. All fatty acids (lubiprostone, cobiprostone, eicosatetraynoic acid (ETYA), oleic acid and elaidic acid) caused significant rightward shifts in concentration-dependent Cl(-) current activation (increasing EC50s) with mutant compared to WT hClC-2 channels, without changing time- and voltage-dependence, I-V rectification or methadone inhibition of the channel...
April 19, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28399886/levels-of-hepatic-th17-cells-and-regulatory-t-cells-upregulated-by-hepatic-stellate-cells-in-advanced-hbv-related-liver-fibrosis
#12
Xiaoyan Li, Yujie Su, Xuefeng Hua, Chan Xie, Jing Liu, Yuehua Huang, Liang Zhou, Min Zhang, Xu Li, Zhiliang Gao
BACKGROUND: Liver fibrosis which mainly occurs upon chronic hepatitis virus infection potentially leads to portal hypertension, hepatic failure and hepatocellular carcinoma. However, the immune status of Th17 and Treg cells in liver fibrosis is controversial and the exact mechanisms remain largely elusive. METHODS: Liver tissues and peripheral blood were obtained simultaneously from 32 hepatitis B virus infected patients undergoing surgery for hepatocellular carcinoma at the medical center of Sun Yat-sen University...
April 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28383418/new-evidence-guiding-extent-of-lymphadenectomy-for-esophagogastric-junction-tumor-application-of-ber-ep4-joint-with-cd44v6-staining-on-the-detection-of-lower-mediastinal-lymph-node-micrometastasis-and-survival-analysis
#13
Bin Zheng, Chen-Hui Ni, Hao Chen, Wei-Dong Wu, Zhao-Hui Guo, Yong Zhu, Wei Zheng, Chun Chen
For Siewert type II adenocarcinoma of the esophagogastric junction (AEJ), the optimal surgical approach and extent of lymph nodes dissection remain controversial. Immunohistochemistry (IHC) has been reported to be available for identifying lymph node micrometastasis (LNMM) in patients with AEJ. This was a prospective case series of patients who underwent R0 resection and lower mediastinal lymphadenectomy from January 2010 to June 2015 in Fujian Medical University Union Hospital for Siewert type II AEJ. The outcomes were analyzed retrospectively...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28377057/synthesis-and-evaluation-of-18-f-labeled-cj-042794-for-imaging-prostanoid-ep4-receptor-expression-in-cancer-with-positron-emission-tomography
#14
Zhengxing Zhang, Joseph Lau, Hsiou-Ting Kuo, Chengcheng Zhang, Nadine Colpo, François Bénard, Kuo-Shyan Lin
The potent and selective prostanoid EP4 receptor antagonist CJ-042794 was radiolabeled with (18)F, and evaluated for imaging EP4 receptor expression in cancer with positron emission tomography (PET). The fluorination precursor, arylboronic acid pinacol ester 4, was prepared in 4 steps with 42% overall yield. (18)F-CJ-042794 was synthesized via a copper-mediated (18)F-fluorination reaction followed by base hydrolysis, and was obtained in 1.5±1.1% (n=2) decay-corrected radiochemical yield. PET/CT imaging and biodistribution studies in mice showed that (18)F-CJ-042794 was excreted through both renal and hepatobiliary pathways with significant retention in blood...
March 27, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28359217/efferocytosis-induced-prostaglandin-e2-production-impairs-alveolar-macrophage-effector-functions-during-streptococcus-pneumoniae-infection
#15
Ana Cg Salina, Tais P Souza, Carlos H Serezani, Alexandra I Medeiros
Alveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined...
April 2017: Innate Immunity
https://www.readbyqxmd.com/read/28342204/the-ep4-antagonist-l-161-982-induces-apoptosis-cell-cycle-arrest-and-inhibits-prostaglandin-e2-induced-proliferation-in-oral-squamous-carcinoma-tca8113-cells
#16
Xiaohui Li, Bo Yang, Guoxu Han, Weizhong Li
BACKGROUND: Recent studies suggest that cyclooxygenase 2 (COX-2) inhibitors may enhance the toxic effects of anticancer drugs on tumor cells, including oral squamous cell carcinoma (OSCC), but its long-term use can cause side effects such as stomach ulcers and myocardial infarction. Our aim was to investigate proliferative effects of a downstream product of COX-2, prostaglandin E2 (PGE2), in human oral squamous carcinoma cell line Tca8113 and explore the effects of PGE2 receptors, especially EP4 receptor, on the growth of Tca8113 cells...
March 25, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28341741/endogenous-prostaglandin-e2-amplifies-il-33-production-by-macrophages-through-an-e-prostanoid-ep-2-ep4-camp-epac-dependent-pathway
#17
Sachin K Samuchiwal, Barbara Balestrieri, Hannah Raff, Joshua A Boyce
When activated through toll-like receptors (TLRs), macrophages generate IL-33, an IL-1 family member that induces innate immune responses through ST2 signaling. LPS, a TLR4 ligand, induces macrophages to generate prostaglandin E2 (PGE2) through inducible COX-2 and microsomal PGE2 synthase 1 (mPGES-1) (1). We demonstrate that IL-33 production by bone marrow-derived murine macrophages (bmMFs) requires the generation of endogenous PGE2 and the intrinsic expression of EP2 receptors to amplify NF-κB-dependent, LPS-induced IL-33 expression via exchange protein activated by cAMP (EPAC)...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28336432/behavioral-abnormalities-and-reduced-norepinephrine-in-ep4-receptor-associated-protein-eprap-deficient-mice
#18
Risako Fujikawa, Sei Higuchi, Taichi Ikedo, Manabu Nagata, Kosuke Hayashi, Tao Yang, Takeshi Miyata, Masayuki Yokode, Manabu Minami
EP4 receptor-associated protein (EPRAP) is a newly identified molecule that regulates macrophage activation. We recently demonstrated the presence of EPRAP in the mice brain; however, little is known about the function of EPRAP in this tissue. Therefore, we investigated the role of EPRAP in behavior and emotion using behavioral analysis in mice. In this study, we subjected EPRAP-deficient (KO) mice and wild-type C57BL/6 (WT) mice to a battery of behavioral tests. EPRAP-KO mice tended to have shorter latencies to fall in the wire hang test, but had normal neuromuscular strength...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28300577/pge2-synthesis-and-signaling-in-malignant-transformation-and-progression-of-human-hepatocellular-carcinoma
#19
Shengbing Zang, Xiaojie Ma, Yanbin Wu, Wenwen Liu, Haili Cheng, Jiasi Li, Jingfeng Liu, Aimin Huang
Prostaglandin E 2 (PGE2), which is the most abundant prostaglandin produced in hepatocellular carcinoma (HCC), may be involved in hepatocarcinogenesis. Here, the amount of PGE2 was significantly increased in HCC tissue and adjacent non-cancerous tissues relative to normal liver tissue (P<.001). In addition, the expression of EP2 receptor was considerably up-regulated in HCC tissue compared with the expression of EP1 (P<.05), EP3 (P<.01), and EP4 (P<.01) receptor. The expression of EP2 receptor was positively correlated with the level of PGE2 in HCC tissue (P<...
March 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28293390/effect-of-sodium-hydrosulfide-on-mrna-expression-of-prostaglandin-e2-receptors-in-response-to-mucosal-acidification-and-distention-induced-gastric-acid-secretion-in-rats
#20
Seyyed Ali Mard, Simin Mahini, Mahin Dianat, Yaghoob Farbood
OBJECTIVES: Prostaglandins have been shown to mediate the gastro-protective effect of sodium hydrosulfide (NaHS) but effect of NaHS on mRNA expression of prostaglandin E2 receptors (EP1, 3-4; EPs) has not been investigated. Therefore, this study designed to evaluate the effect of NaHS on mRNA expression of EPs receptors in response to mucosal acidification and distention-induced gastric acid secretion in rats. MATERIALS AND METHODS: Fasted rats were randomly assigned into 4 groups (n=6/group)...
February 2017: Iranian Journal of Basic Medical Sciences
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