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https://www.readbyqxmd.com/read/28646018/the-amyloid-precursor-protein-modulates-%C3%AE-2a-adrenergic-receptor-endocytosis-and-signaling-through-disrupting-arrestin-3-recruitment
#1
Fang Zhang, Mary Gannon, Yunjia Chen, Lufang Zhou, Kai Jiao, Qin Wang
The amyloid precursor protein (APP) has long been appreciated for its role in Alzheimer's disease (AD) pathology. However, less is known about the physiologic function of APP outside of AD. Particularly, whether and how APP may regulate functions of cell surface receptors, including GPCRs, remains largely unclear. In this study, we identified a novel direct interaction between APP and the α2A adrenergic receptor (α2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with α2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28639248/p2x-receptor-activation
#2
Toshimitsu Kawate
Extracellular ATP-gated P2X receptors are trimeric non-selective cation channels important for many physiological events including immune response and neural transmission. These receptors belong to a unique class of ligand-gated ion channels composed of only six transmembrane helices and a relatively small extracellular domain that harbors three ATP-binding pockets. The crystal structures of P2X receptors, including the recent P2X3 structures representing three different stages of the gating cycle, have provided a compelling structural foundation for understanding how this class of ligand-gated ion channels function...
June 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28637794/a-trpv1-to-secretagogin-regulatory-axis-controls-pancreatic-%C3%AE-cell-survival-by-modulating-protein-turnover
#3
Katarzyna Malenczyk, Fatima Girach, Edit Szodorai, Petter Storm, Åsa Segerstolpe, Giuseppe Tortoriello, Robert Schnell, Jan Mulder, Roman A Romanov, Erzsébet Borók, Fabiana Piscitelli, Vincenzo Di Marzo, Gábor Szabó, Rickard Sandberg, Stefan Kubicek, Gert Lubec, Tomas Hökfelt, Ludwig Wagner, Leif Groop, Tibor Harkany
Ca(2+)-sensor proteins are generally implicated in insulin release through SNARE interactions. Here, secretagogin, whose expression in human pancreatic islets correlates with their insulin content and the incidence of type 2 diabetes, is shown to orchestrate an unexpectedly distinct mechanism. Single-cell RNA-seq reveals retained expression of the TRP family members in β-cells from diabetic donors. Amongst these, pharmacological probing identifies Ca(2+)-permeable transient receptor potential vanilloid type 1 channels (TRPV1) as potent inducers of secretagogin expression through recruitment of Sp1 transcription factors...
June 21, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28637786/the-role-of-capsaicin-sensitive-c-fiber-afferent-pathways-in-the-control-of-micturition-in-spinal-intact-and-spinal-cord-injured-mice
#4
Katsumi Kadekawa, Tsuyoshi Majima, Takahiro Shimizu, Naoki Wada, William C de Groat, Anthony J Kanai, Momokazu Goto, Mitsuharu Yoshiyama, Kimio Sugaya, Naoki Yoshimura
We examined bladder and urethral sphincter activity in mice with or without spinal cord injury (SCI) after C-fiber afferent desensitization induced by capsaicin pretreatment and changes in electrophysiological properties of mouse bladder afferent neurons 4 weeks after SCI. Female C57BL/6N mice were divided into 4 groups; (1) spinal intact (SI)-control, (2) SI-capsaicin pretreatment (Cap), (3) SCI-control and (4) SCI-Cap groups. Continuous cystometry and external urethral sphincter (EUS)-electromyogram (EMG) were conducted under an awake condition...
June 21, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28636912/channeling-of-camp-in-pde-pka-complexes-promotes-signal-adaptation
#5
Nikhil Kumar Tulsian, Srinath Krishnamurthy, Ganesh Srinivasan Anand
Spatiotemporal control of the cAMP signaling pathway is governed by both hormonal stimulation of cAMP generation by adenylyl cyclases (activation phase) and cAMP hydrolysis by phosphodiesterases (PDEs) (termination phase). The termination phase is initiated by PDEs actively targeting the protein kinase A (PKA) R-subunit through formation of a PDE-PKAR-cyclic adenosine monophosphate (cAMP) complex (the termination complex). Our results using PDE8 as a model PDE, reveal that PDEs mediate active hydrolysis of cAMP bound to its receptor RIα by enhancing the enzymatic activity...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28635356/simultaneous-abo-incompatible-living-donor-liver-transplantation-and-splenectomy-without-plasma-exchange-in-china-two-case-reports
#6
Guoyong Chen, Janjun Sun, Sidong Wei, Yongfeng Chen, Gaofeng Tang, Zhantao Xie, Huaen Xu, Janbin Chen, Huibo Zhao, Zhenhua Yuan, Weiwei Wang, Guangbo Liu, Bing Wang, Biao Niu
ABO-incompatible (ABO-i) living-donor liver transplantation (LDLT) is performed if an ABO-compatible graft cannot be obtained. However, a perfect desensitization protocol has not been established worldwide, especially for simultaneous ABO-i LDLT and splenectomy. We herein report two cases of ABO-i LDLT. To the best of our knowledge, this is the first case report of ABO-i LDLT in an adult patient in China. Splenectomy and T-cell-targeted immunosuppression (basiliximab) was used to overcome the blood group barrier in these recipients...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28634772/the-effect-of-desensitization-therapy-in-kidney-transplantation
#7
Yong Chul Kim, Mi-Yeon Yu, Jung Pyo Lee, Hajeong Lee, Sang-Il Min, Jongwon Ha, Yon Su Kim
BACKGROUND: Desensitization therapy may enable the patient to get allograft in sensitized recipient or solve the organ shortage in ABO-incompatible relationship in kidney transplantation (KT). However, the graft outcome and morbidity remains unclear. METHODS: We retrospectively analyzed 845 KT patients from January 2010 to February 2016 at Seoul National University Hospital. The patients were divided into three groups as follows: HLA-incompatible (HLAi) group, ABO-incompatible (ABOi) group, and control group...
June 20, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28632938/mek-inhibitors-induce-akt-activation-and-drug-resistance-by-suppressing-negative-feedback-erk-mediated-her2-phosphorylation-at-thr701
#8
Chia-Hung Chen, Te-Chun Hsia, Ming-Hsin Yeh, Tsung-Wei Chen, Yun-Ju Chen, Jung-Tsu Chen, Ya-Ling Wei, Chih-Yen Tu, Wei-Chien Huang
Targeting the MEK/ERK pathway has been viewed as a promising strategy for cancer therapy. However, MEK inhibition leads to the compensatory PI3K/AKT activation and thus contributes to the desensitization of cancer cells to MEK inhibitors. The underlying molecular mechanism of this event is not yet understood. In this study, our data showed that the induction of Akt activity by MEK inhibitors was specifically observed in HER2-positive breast cancer cells. Silence of HER2, or overexpression of HER2 kinase-dead mutant, prevents the induction of Akt activation in response to MEK inhibition, indicating HER2 as a critical regulator for this event...
June 20, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28632196/drug-hypersensitivity-and-desensitizations-mechanisms-and-new-approaches
#9
REVIEW
Leticia de Las Vecillas Sánchez, Leila A Alenazy, Marlene Garcia-Neuer, Mariana C Castells
Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS)...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28631356/immune-tolerance-effect-in-mesenteric-lymph-node-lymphocytes-of-geniposide-on-adjuvant-arthritis-rats
#10
Zheng-Rong Zhang, Hong Wu, Rong Wang, Shu-Ping Li, Li Dai, Wen-Yu Wang
Rheumatoid arthritis (RA) is a systemic, Th1 cytokine-predominant autoimmune disease result in a chronic and inflammatory disorder. Geniposide (GE), an iridoid glycoside compound that is purified from Gardenia jasminoides Ellis, has antiinflammatory and other immunoregulatory effects, but its exact mechanism of actions on RA is unknown. The aim of this study was to elucidate antiinflammation effects of GE on adjuvant arthritis (AA) rats and its possible immune tolerance mechanisms. Male Sprague-Dawley rats were administered with GE (30, 60, and 120 mg/kg) orally from day 17 to 24 after immunization...
June 19, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28629602/management-of-dentin-hypersensitivity-by-practitioners-in-the-national-dental-practice-based-research-network
#11
Dorota T Kopycka-Kedzierawski, Cyril Meyerowitz, Mark S Litaker, Marc W Heft, Nirmala Tasgaonkar, Marianne R Day, Andretta Porter-Williams, Valeria V Gordan, Robin L Yardic, Timothy M Lawhorn, Gregg H Gilbert
BACKGROUND: Dentin hypersensitivity (DH) is a condition commonly encountered in clinical dental practice. The authors conduct a study to identify the treatments recommended to manage DH among dentists in the United States. METHODS: The authors conducted a multicenter study of 1,862 patients with DH who received a diagnosis and were treated by 171 dentists with the National Dental Practice-Based Research Network. RESULTS: The most common treatment recommended was desensitizing over-the-counter (OTC) potassium nitrate toothpaste (alone or in combination with other treatments) for 924 of 1,862 patients (50%)...
June 16, 2017: Journal of the American Dental Association
https://www.readbyqxmd.com/read/28629321/the-biocontrol-agent-pseudomonas-chlororaphis-pa23-primes-brassica-napus-defenses-through-distinct-gene-networks
#12
Kelly A Duke, Michael G Becker, Ian J Girard, Jenna L Millar, W G Dilantha Fernando, Mark F Belmonte, Teresa R de Kievit
BACKGROUND: The biological control agent Pseudomonas chlororaphis PA23 is capable of protecting Brassica napus (canola) from the necrotrophic fungus Sclerotinia sclerotiorum via direct antagonism. While we have elucidated bacterial genes and gene products responsible biocontrol, little is known about how the host plant responds to bacterial priming on the leaf surface, including global changes in gene activity in the presence and absence of S. sclerotiorum. RESULTS: Application of PA23 to the aerial surfaces of canola plants reduced the number of S...
June 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28626043/the-diverse-roles-of-arrestin-scaffolds-in-g-protein-coupled-receptor-signaling
#13
REVIEW
Yuri K Peterson, Louis M Luttrell
The visual/β-arrestins, a small family of proteins originally described for their role in the desensitization and intracellular trafficking of G protein-coupled receptors (GPCRs), have emerged as key regulators of multiple signaling pathways. Evolutionarily related to a larger group of regulatory scaffolds that share a common arrestin fold, the visual/β-arrestins acquired the capacity to detect and bind activated GPCRs on the plasma membrane, which enables them to control GPCR desensitization, internalization, and intracellular trafficking...
July 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28625142/proteotoxic-stress-desensitizes-tgf-beta-signaling-through-receptor-downregulation-in-retinal-pigment-epithelial-cells
#14
X Tan, C Chen, Y Zhu, J Deng, X Qiu, S Huang, F Shang, B Cheng, Y Liu
BACKGROUND: Transforming growth factor (TGFβ)-induced epithelial-mesenchymal transition (EMT) and proteotoxic stress are two main contributors of intraocular fibrotic disorders, including proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). However, how these two factors communicate with each other is not well-characterized. OBJECTIVE: The aim was to investigate the regulatory role of proteotoxic stress on TGFβ signaling in retinal pigment epithelium...
June 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28624610/anti-fc%C3%AE-riib-monoclonal-antibody-suppresses-murine-igg-dependent-anaphylaxis-by-fc-domain-targeting-of-fc%C3%AE-riii
#15
Corey D Clay, Richard T Strait, Ashley Mahler, Marat V Khodoun, Fred D Finkelman
BACKGROUND: The inhibitory receptor, FcγRIIB, is expressed on human and murine bone marrow-derived cells and limits inflammation by suppressing signaling through stimulatory receptors. OBJECTIVE: Evaluate the effects of K9.361, a mouse IgG2a alloantibody to mouse FcγRIIB, on murine anaphylaxis. METHODS: Wild-type and FcγR-deficient mice were used to study anaphylaxis, which was induced by injection of 2.4G2 (rat IgG2b mAb that binds both FcγRIIB and the stimulatory receptor, FcγRIII); by actively immunizing IgE-deficient mice, then challenging with the immunizing Ag; and by passive immunization with IgG or IgE anti-TNP mAb, followed by injection of TNP-ovalbumin...
June 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28620648/effect-of-fc-%C3%AE-receptor-polymorphism-on-rituximab-mediated-b-cell-depletion-in-abo-incompatible-adult-living-donor-liver-transplantation
#16
Hiroshi Sakai, Yuka Tanaka, Hirofumi Tazawa, Seiichi Shimizu, Sapana Verma, Masahiro Ohira, Hiroyuki Tahara, Kentaro Ide, Kohei Ishiyama, Tsuyoshi Kobayashi, Takashi Onoe, Hideki Ohdan
BACKGROUND: The affinity of IgG Fc receptor (FcγR) for rituximab, an anti-CD20 IgG1, differs based on single-nucleotide polymorphisms (SNPs) in FcγRs. This study aimed to explore the effect of such SNPs on clinical response to rituximab and outcomes in patients of ABO-incompatible (ABOi) living donor liver transplantation (LDLT). METHODS: SNPs of FCGR2A[131H/R] and FCGR3A[158F/V], alleles encoding FcγR, were identified in 20 patients desensitized with rituximab before ABOi LDLT...
June 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28619996/farnesoid-x-receptor-and-liver-x-receptor-ligands-initiate-formation-of-coated-platelets
#17
Amanda J Unsworth, Alexander P Bye, Dionne S Tannetta, Michael J R Desborough, Neline Kriek, Tanya Sage, Harriet E Allan, Marilena Crescente, Parveen Yaqoob, Timothy D Warner, Chris I Jones, Jonathan M Gibbins
OBJECTIVES: The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28619258/rho-kinase-dependent-desensitization-of-gpr39-a-unique-mechanism-of-gpcr-downregulation
#18
Yuji Shimizu, Ryokichi Koyama, Tomohiro Kawamoto
GPR39, a G-protein-coupled receptor activated by zinc, reportedly activates multiple intracellular signaling pathways via Gs, Gq, G12/13, and β-arrestin, but little is known about downregulation of the receptor upon its activation. To our knowledge, this is the first report on the mechanism of feedback regulation of GPR39 function determined in GPR39-expressing HEK293 cells (HEK293-GPR39) as a model cell system. In HEK293-GPR39 cells, GPR39-C3, which is a positive allosteric modulator, activated cAMP production (downstream of Gs), IP1 accumulation (downstream of Gq), SRF-RE-dependent transcription (downstream of G12/13), and β-arrestin recruitment...
June 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28616989/reconstructed-serine288-in-the-left-flipper-region-of-rat-p2x7-receptor-stabilizes-non-sensitized-states
#19
Yevheniia Ishchenko, Nataliia Novosolova, Kamil Khafizov, Genevieve Bart, Arina Timonina, Dmitriy Fayuk, Andrei Skorinkin, Rashid Giniatullin
Serine 275, a conserved residue of the left flipper region of ATP-gated P2X3 receptors, plays a key role in both agonist binding and receptor desensitization. It is conserved in most of the P2X receptors except P2X7 and P2X6. By combining experimental patch-clamp and modelling approaches, we explored the role of the corresponding residue in rat P2X7 receptor (rP2X7) by replacing phenylalanine in the position 288 with serine and characterizing the membrane currents generated by either WT or mutated rP2X7 receptor...
June 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28614234/motion-based-equilibrium-reprocessing-therapy-a-novel-treatment-method-for-chronic-peripheral-vestibulopathies-a-pilot-study
#20
Mirke S Hondebrink, Agali Mert, Roos van der Lint, J Alexander de Ru, Peter van der Wurff
Rehabilitation for vestibular disease is a safe method to partially alleviate symptoms of vertigo. It was hypothesized that principles of military aviation vestibular desensitization procedures that have a success rate of more than 80% can be extrapolated to chronic vestibular disease as well.The virtual reality motion base computer-assisted rehabilitation environment was used as treatment modality in 17 patients. They were exposed to sinusoidal vertical passive whole body motion in increasing intensity for a maximum of 12 sessions...
June 2017: Medicine (Baltimore)
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