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https://www.readbyqxmd.com/read/28874459/protease-activated-receptor-2-activates-airway-apical-membrane-chloride-permeability-and-increases-ciliary-beating
#1
Derek B McMahon, Alan D Workman, Michael A Kohanski, Ryan M Carey, Jenna R Freund, Benjamin M Hariri, Bei Chen, Laurel J Doghramji, Nithin D Adappa, James N Palmer, David W Kennedy, Robert J Lee
Mucociliary clearance, driven by the engine of ciliary beating, is the primary physical airway defense against inhaled pathogens and irritants. A better understanding of the regulation of ciliary beating and mucociliary transport is necessary for identifying new receptor targets to stimulate improved clearance in airway diseases, such as cystic fibrosis and chronic rhinosinusitis. In this study, we examined the protease-activated receptor (PAR)-2, a GPCR previously shown to regulate airway cell cytokine and mucus secretion, and transepithelial Cl(-) current...
September 5, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28759536/ranking-prediction-model-using-the-competition-record-of-ladies-professional-golf-association-players
#2
Jin Seok Chae, Jin Park, Wi-Young So
The purpose of this study was to suggest a ranking prediction model using the competition record of the Ladies Professional Golf Association (LPGA) players. The top 100 players on the tour money list from the 2013-2016 US Open were analyzed in this model. Stepwise regression analysis was conducted to examine the effect of performance and independent variables (i.e., driving accuracy, green in regulation, putts per round, driving distance, percentage of sand saves, par-3 average, par-4 average, par-5 average, birdies average, and eagle average) on dependent variables (i...
July 28, 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/28720068/inhibitory-effect-of-par-4-combined-with-cisplatin-on-human-wilms-tumor-cells
#3
Jun Wang, Yunjie Li, Fangfang Ma, Huifeng Zhou, Rong Ding, Binbin Lu, Li Zou, Junxia Li, Rugang Lu
Wilms' tumor is associated with a high treatment success rate, but there is still a risk of recurrence. Cisplatin, which is one of the chemotherapeutic agents used for its treatment, is associated with a very high rate of resistance. Par-4 (prostate apoptosis response 4) is a tumor suppressor, which is capable of sensitizing tumor cells to chemotherapy. Therefore, the aim of this study was to determine whether combined treatment with Par-4 and cisplatin is effective for inhibiting growth of Wilms' tumor. Wilms' tumor and control cell samples were collected and analyzed by immunofluorescence assay and immunohistochemistry...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28647672/therapeutic-targeting-of-nuclear-export-inhibition-in-lung-cancer
#4
Arjun Gupta, Jessica M Saltarski, Michael A White, Pier P Scaglioni, David E Gerber
Intracellular compartmentalization and trafficking of molecules plays a critical role in complex and essential cellular processes. In lung cancer and other malignancies, aberrant nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators results in tumorigenesis and inactivation of apoptosis. Pharmacologic agents targeting this process, termed selective inhibitors of nuclear export (SINE), have demonstrated antitumor efficacy in preclinical models and human clinical trials. Exportin-1 (XPO1), which serves as the sole exporter of several tumor suppressor proteins and cell cycle regulators, including retinoblastoma, adenomatous polyposis coli, p53, p73, p21, p27, forkhead box O, signal transducer and activator of transcription 3, inhibitor of κB, topoisomerase II, and protease activated receptor 4-is the principal focus of development of SINE...
September 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28625975/a-naturally-generated-decoy-of-the-prostate-apoptosis-response-4-protein-overcomes-therapy-resistance-in-tumors
#5
Nikhil Hebbar, Ravshan Burikhanov, Nidhi Shukla, Shirley Qiu, Yanming Zhao, Kojo S J Elenitoba-Johnson, Vivek M Rangnekar
Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth...
August 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28623607/presenilin-1-targeted-morpholino-induces-cognitive-deficits-increased-brain-a%C3%AE-1-42-and-decreased-synaptic-marker-psd-95-in-zebrafish-larvae
#6
Laura Roesler Nery, Natalia Eltz Silva, Raphaela Fonseca, Monica Ryff Moreira Vianna
Presenilins are transmembrane proteases required for the proteolytic cleavage of Notch and also act as the catalytic core of the γ-secretase complex, which is responsible for the final cleavage of the amyloid precursor protein into Amyloid-β (Aβ) peptides of varying lengths. Presenilin-1 gene (psen1) mutations are the main cause of early-onset autosomal-dominant Familial Alzheimer Disease. Elucidating the roles of Presenilin-1 and other hallmark proteins involved in Alzheimer's disease is crucial for understanding the disease etiology and underlying molecular mechanisms...
June 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28622290/structural-basis-for-the-regulatory-interactions-of-proapoptotic-par-4
#7
Udaya K Tiruttani Subhramanyam, Jan Kubicek, Ulf B Eidhoff, Joerg Labahn
Par-4 is a unique proapoptotic protein with the ability to induce apoptosis selectively in cancer cells. The X-ray crystal structure of the C-terminal domain of Par-4 (Par-4CC), which regulates its apoptotic function, was obtained by MAD phasing. Par-4 homodimerizes by forming a parallel coiled-coil structure. The N-terminal half of Par-4CC contains the homodimerization subdomain. This structure includes a nuclear export signal (Par-4NES) sequence, which is masked upon dimerization indicating a potential mechanism for nuclear localization...
September 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28530706/akt-is-indispensable-for-coordinating-par-4-jnk-cross-talk-in-p21-downmodulation-during-er-stress
#8
R U Rasool, D Nayak, S Chakraborty, M M Faheem, B Rah, P Mahajan, V Gopinath, A Katoch, Z Iqra, S K Yousuf, D Mukherjee, L D Kumar, A Nargotra, A Goswami
The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28494348/withaferin-a-inhibits-prostate-carcinogenesis-in-a-pten-deficient-mouse-model-of-prostate-cancer
#9
Jim Moselhy, Suman Suman, Mohammed Alghamdi, Balaji Chandarasekharan, Trinath P Das, Alatassi Houda, Murali Ankem, Chendil Damodaran
We recently demonstrated that AKT activation plays a role in prostate cancer progression and inhibits the pro-apoptotic function of FOXO3a and Par-4. AKT inhibition and Par-4 induction suppressed prostate cancer progression in preclinical models. Here, we investigate the chemopreventive effect of the phytonutrient Withaferin A (WA) on AKT-driven prostate tumorigenesis in a Pten conditional knockout (Pten-KO) mouse model of prostate cancer. Oral WA treatment was carried out at two different doses (3 and 5 mg/kg) and compared to vehicle over 45 weeks...
May 7, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28475617/regulation-of-the-pi3k-akt-pathway-during-decidualization-of-endometrial-stromal-cells
#10
François Fabi, Kathy Grenier, Sophie Parent, Pascal Adam, Laurence Tardif, Valérie Leblanc, Eric Asselin
Infertility is constantly increasing in Canada, where 16% of Canadian couples are experiencing difficulty conceiving. It is thought that infertility can emanate from the dysregulated communication between the embryo and the maternal endometrium. In order to allow for this window of implantation to be open at the right moment, endometrial stromal cells proliferate and differentiate by a mechanism called decidualization. Intracellular and molecular mechanisms involved in the regulation of apoptosis and cell proliferation during decidualization of the endometrium are yet to be fully understood...
2017: PloS One
https://www.readbyqxmd.com/read/28460264/flow-cytometry-analysis-reveals-different-activation-profiles-of-thrombin-or-trap-stimulated-platelets-in-db-db-mice-the-regulatory-role-of-par-3
#11
Hassan Kassassir, Karolina Siewiera, Marcin Talar, Tomasz Przygodzki, Cezary Watala
INTRODUCTION: Recent studies have shown that it may be the concentration of thrombin, which is discriminative in determining of the mechanism of platelet activation via protease activated receptors (PARs). Whether the observed phenomenon of differentiated responses of mouse platelets to various thrombin concentrations in non-diabetic db/+ and diabetic db/db mice depends upon the concerted action of various PARs, remains to be established. RESULTS: We found elevated reactivity of platelets, as well as the enhanced PAR-3 expression in response to both the used concentrations of AYPGKF in db/db mice, as compared to db/+ heterozygotes...
June 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28448853/a-cluster-of-aspartic-residues-in-the-extracellular-loop-ii-of-par-4-is-important-for-thrombin-interaction-and-activation-of-platelets
#12
Daniel Sánchez Centellas, Sushanth Gudlur, Alejandro Vicente-Carrillo, Sofia Ramström, Tomas L Lindahl
Thrombin activates platelets via proteolytic cleavage of protease-activated receptors (PARs) 1 and 4. The two PARs have distinct but complementary roles. The mechanisms responsible for PAR1 activation by thrombin have been extensively studied. However, much less is known regarding thrombin activation of PAR4, especially the potential involvement of regions of PAR4 other than the N-terminal, which is bound to the catalytic site of thrombin. We have studied PAR4 in S. cerevisiae strain MMY12, an expression system in which the GPCR receptors are connected to a Lac Z reporter gene resulting in increased β-galactosidase activity...
April 13, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28410423/daf-18-pten-signals-through-aak-1-ampk-to-inhibit-mpk-1-mapk-in-feedback-control-of-germline-stem-cell-proliferation
#13
Patrick Narbonne, Paul S Maddox, Jean-Claude Labbé
Under replete growth conditions, abundant nutrient uptake leads to the systemic activation of insulin/IGF-1 signalling (IIS) and the promotion of stem cell growth/proliferation. Activated IIS can stimulate the ERK/MAPK pathway, the activation of which also supports optimal stem cell proliferation in various systems. Stem cell proliferation rates can further be locally refined to meet the resident tissue's need for differentiated progeny. We have recently shown that the accumulation of mature oocytes in the C...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28267389/molecular-requirements-involving-the-human-platelet-protease-activated-receptor-4-mechanism-of-activation-by-peptide-analogues-of-its-tethered-ligand
#14
I C Moschonas, T F Kellici, T Mavromoustakos, P Stathopoulos, V Tsikaris, V Magafa, A G Tzakos, A D Tselepis
Thrombin is the most potent agonist of human platelets and its effects are primarily mediated through the protease-activated receptors (PARs)-1 and -4. Although PAR-1 has higher affinity for thrombin than PAR-4, both receptors contribute to thrombin-mediated actions on platelets. Recently, a potent and selective PAR-1 antagonist (vorapaxar) was approved for clinical use in selected patients. In contrast, despite the fact that several PAR-4 antagonists have been developed, few of them have been tested in clinical trials...
March 7, 2017: Platelets
https://www.readbyqxmd.com/read/28076793/chloroquine-inducible-par-4-secretion-is-essential-for-tumor-cell-apoptosis-and-inhibition-of-metastasis
#15
Ravshan Burikhanov, Nikhil Hebbar, Sunil K Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S Watt, Danny R Welch, Jodi Maranchie, Akihiro Harada, Vivek M Rangnekar
The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28008141/chemoresistance-and-targeted-therapies-in-ovarian-and-endometrial-cancers
#16
Kevin Brasseur, Nicolas Gévry, Eric Asselin
Gynecological cancers are known for being very aggressive at their advanced stages. Indeed, the survival rate of both ovarian and endometrial cancers is very low when diagnosed lately and the success rate of current chemotherapy regimens is not very efficient. One of the main reasons for this low success rate is the acquired chemoresistance of these cancers during their progression. The mechanisms responsible for this acquired chemoresistance are numerous, including efflux pumps, repair mechanisms, survival pathways (PI3K/AKT, MAPK, EGFR, mTOR, estrogen signaling) and tumor suppressors (P53 and Par-4)...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/27995367/paracoccidioides-brasiliensis-induces-cytokine-secretion-in-epithelial-cells-in-a-protease-activated-receptor-dependent-par-manner
#17
Priscila de Oliveira, Maria Aparecida Juliano, Aparecida Sadae Tanaka, Adriana Karaoglanovic Carmona, Saara Maria Batista Dos Santos, Bianca Carla Silva Campitelli de Barros, Paloma Korehisa Maza, Rosana Puccia, Erika Suzuki
Paracoccidioides brasiliensis is one of the etiological agents of the human systemic mycosis paracoccidioidomycosis. Protease-activated receptors (PARs) are expressed in many cell types and comprise a family of G protein-coupled receptors (PAR-1, PAR-2, and PAR-4), which may be activated by proteases secreted by several pathogens. In the present study, we showed that the pathogenic fungus P. brasiliensis secretes components that promote interleukin (IL)-6 and IL-8 secretion by the lung epithelial cell line A549...
April 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/27992120/dabigatran-enhances-platelet-reactivity-and-platelet-thrombin-receptor-expression-in-patients-with-atrial-fibrillation
#18
A Achilles, A Mohring, L Dannenberg, M Grandoch, T Hohlfeld, J W Fischer, B Levkau, M Kelm, T Zeus, A Polzin
Essentials Whether or not dabigatran enhances the risk of myocardial infarction is under discussion. We measured platelet reactivity and thrombin receptor expression in dabigatran patients. Platelet reactivity and thrombin receptor expression is enhanced during dabigatran treatment. This should be considered when choosing the optimal direct oral anticoagulant for individuals. SUMMARY: Background The direct oral anticoagulant (DOAC) dabigatran is a direct thrombin inhibitor. Its landmark trial, the RE-LY study, observed a trend towards a higher incidence of myocardial infarctions (MIs) in dabigatran-treated patients...
March 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27901488/cancer-associated-fibroblasts-promote-cancer-cell-growth-through-a-mir-7-rassf2-par-4-axis-in-the-tumor-microenvironment
#19
Zongze Shen, Xing Qin, Ming Yan, Rongrong Li, Gang Chen, Jianjun Zhang, Wantao Chen
Cancer-associated fibroblasts (CAFs), a major component of cancer stroma, play an important role in cancer progression but little is known about how CAFs affect tumorigenesis and development. MicroRNAs (miRNAs) are small non-coding RNAs that can negatively regulate target mRNA expression at post-transcriptional levels. In head and neck cancer (HNC), our analysis of miRNA arrays showed that miR-7, miR-196 and miR-335 were significantly up-regulated in CAFs when compared with their paired normal fibroblasts (NFs)...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27890308/erratum-to-a-combined-deficiency-of-tissue-factor-and-par-4-is-associated-with-fatal-pulmonary-hemorrhage-in-mice-thromb-res-146-2016-46-50
#20
Michael F Bode, Nigel Mackman
No abstract text is available yet for this article.
January 2017: Thrombosis Research
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