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https://www.readbyqxmd.com/read/28759126/ep2-receptor-plays-pivotal-roles-in-generating-mechanical-hyperalgesia-after-lengthening-contraction
#1
Hiroki Ota, Kimiaki Katanosaka, Shiori Murase, Tomoyuki Furuyashiki, Shuh Narumiya, Kazue Mizumura
INTRODUCTION: We previously demonstrated that nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) were upregulated after lengthening contraction (LC) in exercised muscle through B2 bradykinin receptor activation and cyclooxygenase (COX)-2 upregulation, respectively, and that these trophic factors sensitized nociceptors resulting in mechanical hyperalgesia (delayed-onset muscle soreness, DOMS). Here we examined the prostaglandin receptor subtype involved in DOMS...
July 31, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28753926/the-prostaglandin-ep3-receptor-is-an-independent-negative-prognostic-factor-for-cervical-cancer-patients
#2
Helene Heidegger, Sebastian Dietlmeier, Yao Ye, Christina Kuhn, Aurelia Vattai, Caroline Aberl, Udo Jeschke, Sven Mahner, Bernd Kost
We know that one of the main risk factors for cervical cancer is an infection with high-risk human papillomavirus (HR-HPV). Prostaglandins and their receptors are very important for the tumour growth and tumour-associated angiogenesis. Little is known about the expression of the Prostaglandin E receptor type 3 (EP3) or the Prostaglandin (PG)E₂-EP3 signalling in cervical cancer, so the aim of the study was to analyse the expression of the EP3 receptor in cervical cancer and find prognostic factors in relation to survival; EP3 immunohistological staining of 250 cervical cancer slides was performed and analysed with a semi-quantitative score...
July 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28710231/tuberin-regulates-prostaglandin-receptor-mediated-viability-via-rheb-in-mtorc1-hyperactive-cells
#3
Chenggang Li, Xiaolei Liu, Yang Liu, Erik Zhang, Kantha Medepalli, Kohei Masuda, Na Li, Elizabeth J Kopras, David J Kwiatkowski, Michael T Borchers, Kathryn A Wikenheiser-Brokamp, Andrew Osterburg, Maxwell Mays, Yang Sun, David R Plas, Julia L Sun, David N Franz, Jamie K Capal, Anya Alayev, Marina K Holz, Darcy A Krueger, Brian J Siroky, Jane J Yu
Tuberous sclerosis complex (TSC) is a tumor suppressor syndrome affecting multiple organs, including the brain, skin, kidneys, heart, and lungs. TSC is associated with mutations in TSC1 or TSC2 resulting in hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1). Clinical trials demonstrate that mTORC1 inhibitors decrease tumor volume and stabilize lung function in TSC patients; however, mTOR inhibitors are cytostatic not cytocidal, and long-term benefits and toxicities are uncertain. Previously, we identified rapamycin-insensitive upregulation of cyclooxygenase 2 (PTGS2/COX2) and prostaglandin E2 (PGE2) production in TSC2-deficient cells and postulate that the action of excess PGE2 and its cognate receptors (EPs) contribute to cell survival...
July 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28701311/pge2-upregulates-renin-through-e-prostanoid-receptor-1-via-pkc-camp-creb-pathway-in-m-1-cells
#4
Alexis A Gonzalez, Nicolas Salinas-Parra, Dan Leach, L Gabriel Navar, Minolfa C Prieto
During the early phase of angiotensin (ANG) II-dependent hypertension tubular prostaglandin E2 (PGE2) is increased. Renin synthesis and secretion in the collecting duct (CD) is upregulated by ANGII contributing to further intratubular ANGII formation. However, what happens first and whether the triggering mechanism is independent of tubular ANGII, remain unknown. PGE2 stimulates renin synthesis in juxtaglomerular (JG) cells via E-prostanoid (EP) receptors through cAMP/CREB pathway. EP receptors are also expressed in the CD...
July 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28699682/2-3-7-8-tetrachlorodibenzo-p-dioxin-promotes-endothelial-cell-apoptosis-through-activation-of-ep3-p38mapk-bcl-2-pathway
#5
Yu Yu, Qian Liu, Shumin Guo, Qianqian Zhang, Juan Tang, Guizhu Liu, Deping Kong, Juanjuan Li, Shuai Yan, Ruiguo Wang, Peilong Wang, Xiaoou Su, Ying Yu
Endothelial injury or dysfunction is an early event in the pathogenesis of atherosclerosis. Epidemiological and animal studies have shown that 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure increases morbidity and mortality from chronic cardiovascular diseases, including atherosclerosis. However, whether or how TCDD exposure causes endothelial injury or dysfunction remains largely unknown. Cultured human umbilical vein endothelial cells (HUVECs) were exposed to different doses of TCDD, and cell apoptosis was examined...
July 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28695379/expression-of-prostaglandin-e2-receptor-subtypes-in-human-pterygium-and-normal-conjunctiva-immunohistochemical-study
#6
Erdem Dinç, Özer Dursun, Banu Yılmaz, Mustafa Vatansever, A Ayça Sarı, Özlem Yıldırım, Ufuk Adıgüzel
PURPOSE: In the present study, we aimed to evaluate the expression of EP receptors in primary and recurrent human pterygium tissues. METHODS: Pterygium samples were collected from 65 patients with primary pterygium and 16 patients with recurrent pterygium. Normal conjunctival tissues were collected from nasal interpalpebral area from 17 patients without systemic and any other ocular pathology. Expression of EP receptors was evaluated by immunohistochemistry. The median value for each receptor staining score (RSS) was determined in normal conjunctival specimens...
July 10, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28687401/pathophysiological-role-of-prostaglandin-e2-induced-up-regulation-of-the-ep2-receptor-in-motor-neuron-like-nsc-34-cells-and-lumbar-motor-neurons-in-als-model-mice
#7
Yasuhiro Kosuge, Hiroko Miyagishi, Yuki Yoneoka, Keiko Yoneda, Hiroshi Nango, Kumiko Ishige, Yoshihisa Ito
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of motor neurons. The primary triggers for motor neuronal death are still unknown, but inflammation is considered to be an important factor contributing to the pathophysiology of ALS both clinically and in ALS models. Prostaglandin E2 (PGE2) and its corresponding four E-prostanoid receptors play a pivotal role in the degeneration of motor neurons in human and transgenic models of ALS. It has also been shown that PGE2-EP2 signaling in glial cells (astrocytes or microglia) promotes motor neuronal death in G93A mice...
July 4, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28685234/prostanoid-ep3-receptor-agonist-sulprostone-enhances-pacemaker-activity-of-colonic-interstitial-cells-of-cajal
#8
Man Woo Kim, Han Yi Jiao, Seok Won Kim, Chan Guk Park, Mei Jin Wu, Chansik Hong, Seok Choi, Jae Yeoul Jun
EP receptor activation by PGE2 regulates gastrointestinal motility by modulating smooth muscle contractility. Interstitial cells of Cajal (ICCs) are pacemaker cells that regulate smooth muscle activity. We aimed to determine effects of the EP3 receptor agonist sulprostone on pacemaker potentials in colonic ICCs. We performed a whole cell patch clamp, RT-PCR, and Ca(2+) imaging in cultured ICCs from mouse colon. Sulprostone depolarized the membrane and increased pacemaker frequency. EP3 receptor antagonist blocked these sulprostone-induced effects...
July 6, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28632424/the-progress-in-the-research-of-antiplatelet-agents-1995-2017
#9
Oscar Benimana, Lulu Zhao, Yi Kong, Zhiyu Li, Zhouling Xie
Antiplatelet therapy displays a critical role in the treatment and prevention of antithrombotic disorders. Many new antiplatelet agents have been developed following the emergence of various clinical limitations of classical antiplatelet drugs. This review covers mainly the recent advances in the development of P2Y12 antagonists and GPIIb/IIIa antagonists. Meanwhile, it summarizes promising approaches to new platelet surface receptors such as prostanoid EP3 receptor, thromboxane A2 prostanoid receptor, protease-activated receptors, GPIb-IX-V receptor and P-selectin...
June 20, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28630103/up-regulation-of-ep2-and-ep3-receptors-in-human-tolerogenic-dendritic-cells-boost-the-immunosuppressive-activity-of-pge2
#10
Georgina Flórez-Grau, Raquel Cabezón, Kyra J E Borgman, Carolina España, Juan Jose Lozano, Maria F Garcia-Parajo, Daniel Benítez-Ribas
Dendritic cells (DCs) are APCs essential in regulating the immune response. PGE2, produced during inflammation, has a pivotal role in the maturation of DCs and, therefore, is vital for the immune response. The large variety of biologic functions governed by PGE2 is mediated by its signaling through 4 distinct E-type prostanoid (EP) receptors. Immunogenic DCs express EP2 and EP4, which mediate the PGE2 signaling. However, the expression and function of EP receptors in human tolerogenic DCs (tol-DCs), which present an inhibitory phenotype, have not yet, to our knowledge, been assessed...
June 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28584908/the-ep3-receptor-gz-signaling-axis-as-a-therapeutic-target-for-diabetes-and-cardiovascular-disease
#11
Michael D Schaid, Jaclyn A Wisinski, Michelle E Kimple
Cardiovascular disease is a common co-morbidity found with obesity-linked type 2 diabetes. Current pharmaceuticals for these two diseases treat each of them separately. Yet, diabetes and cardiovascular disease share molecular signaling pathways that are increasingly being understood to contribute to disease pathophysiology, particularly in pre-clinical models. This review will focus on one such signaling pathway: that mediated by the G protein-coupled receptor, Prostaglandin E2 Receptor 3 (EP3), and its associated G protein in the insulin-secreting beta-cell and potentially the platelet, Gz...
June 5, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28580285/opposing-effects-of-prostaglandin-e2-receptors-ep3-and-ep4-on-mouse-and-human-%C3%AE-cell-survival-and-proliferation
#12
Bethany A Carboneau, Jack A Allan, Shannon E Townsend, Michelle E Kimple, Richard M Breyer, Maureen Gannon
OBJECTIVE: Hyperglycemia and systemic inflammation, hallmarks of Type 2 Diabetes (T2D), can induce the production of the inflammatory signaling molecule Prostaglandin E2 (PGE2) in islets. The effects of PGE2 are mediated by its four receptors, E-Prostanoid Receptors 1-4 (EP1-4). EP3 and EP4 play opposing roles in many cell types due to signaling through different G proteins, Gi and GS, respectively. We previously found that EP3 and EP4 expression are reciprocally regulated by activation of the FoxM1 transcription factor, which promotes β-cell proliferation and survival...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28440186/the-double-roles-of-the-prostaglandin-e2-ep2-receptor-in-intracerebral-hemorrhage
#13
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/28439968/effects-of-an-ep2-and-ep3-receptor-dual-agonist-ono-8055-on-a-radical-hysterectomy-induced-underactive-bladder-model-in-monkeys
#14
Hidekazu Matsuya, Noritoshi Sekido, Jun Kida, Hiroko Mashimo, Daisuke Wakamatsu, Hiroki Okada
OBJECTIVES: The objective was to develop an underactive bladder (UAB) model in primates and to evaluate the potential of prostanoid EP2 and EP3 receptor dual agonist ONO-8055 to become a therapeutic agent for UAB. METHODS: A surgical procedure resembling radical hysterectomy was performed on female cynomolgus monkeys. Subsequently, in vitro muscle strip studies were performed using bladder muscle strips from normal monkeys and monkeys that underwent surgery. In addition, uroflowmetric data were obtained at specified days after the surgery...
April 25, 2017: Lower Urinary Tract Symptoms
https://www.readbyqxmd.com/read/28438967/immune-induced-fever-is-dependent-on-local-but-not-generalized-prostaglandin-e2-synthesis-in-the-brain
#15
Anna Eskilsson, Takashi Matsuwaki, Kiseko Shionoya, Elahe Mirrasekhian, Joanna Zajdel, Markus Schwaninger, David Engblom, Anders Blomqvist
Fever occurs upon binding of prostaglandin E2 (PGE2) to EP3 receptors in the median preoptic nucleus of the hypothalamus, but the origin of the pyrogenic PGE2 has not been clearly determined. Here, using mice of both sexes, we examined the role of local versus generalized PGE2 production in the brain for the febrile response. In wild-type mice and in mice with genetic deletion of the prostaglandin synthesizing enzyme cyclooxygenase-2 in the brain endothelium, generated with an inducible CreER(T2) under the Slco1c1 promoter, PGE2 levels in the CSF were only weakly related to the magnitude of the febrile response, whereas the PGE2 synthesizing capacity in the hypothalamus, as reflected in the levels of cyclooxygenase-2 mRNA, showed strong correlation with the immune-induced fever...
May 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28425078/involvement-of-interstitial-cells-of-cajal-in-bladder-dysfunction-in-mice-with-experimental-autoimmune-encephalomyelitis
#16
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...
August 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28423583/the-protection-of-meloxicam-against-chronic-aluminium-overload-induced-liver-injury-in-rats
#17
Yang Yang, Qin He, Hong Wang, Xinyue Hu, Ying Luo, Guojuan Liang, Shengnan Kuang, Shaoshan Mai, Jie Ma, Xiaoyan Tian, Qi Chen, Junqing Yang
The present study was designed to observe the protective effect and mechanisms of meloxicam on liver injury caused by chronic aluminium exposure in rats. The histopathology was detected by hematoxylin-eosin staining. The levels of prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases-2, prostaglandin E2 receptors and protein kinase A were measured by western blotting and immunohistochemistry. Our experimental results showed that aluminium overload significantly damaged the liver...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415726/pge2-ep3-src-signaling-induces-egfr-nuclear-translocation-and-growth-through-egfr-ligands-release-in-lung-adenocarcinoma-cells
#18
Lorenzo Bazzani, Sandra Donnini, Federica Finetti, Gerhard Christofori, Marina Ziche
Prostaglandin E2 (PGE2) interacts with tyrosine kinases receptor signaling in both tumor and stromal cells supporting tumor progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC) cells, A549 and GLC82, PGE2 promotes nuclear translocation of epidermal growth factor receptor (nEGFR), affects gene expression and induces cell growth. Indeed, cyclin D1, COX-2, iNOS and c-Myc mRNA levels are upregulated following PGE2 treatment. The nuclear localization sequence (NLS) of EGFR as well as its tyrosine kinase activity are required for the effect of PGE2 on nEGFR and downstream signaling activities...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415673/camp-pka-creb-bdnf-signaling-pathway-in-hippocampus-mediates-cyclooxygenase-2-induced-learning-memory-deficits-of-rats-subjected-to-chronic-unpredictable-mild-stress
#19
Ying Luo, Shengnan Kuang, Huan Li, Dongzhi Ran, Junqing Yang
To investigate the mechanism of cyclooxygenase 2 (COX2) in learning and memory impairments in rats subjected to chronic unpredictable mild stress (CUMS), meloxicam was used intragastrically to inhibit the activity of cyclooxygenase 2. Moreover, cyclooxygenase 2 over-expressing or RNA interfere lentivirus was injected intraventricularly to increase or decrease the enzyme's expression, respectively. The body weights and sucrose consumption were used to analyze depressive behaviors, while the Morris water maze and step-down-type passive avoidance tests were carried out to evaluate the learning-memory functions...
May 30, 2017: Oncotarget
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
#20
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
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