keyword
https://read.qxmd.com/read/38524121/gpr41-and-gpr43-regulate-cd8-t-cell-priming-during-herpes-simplex-virus-type-1-infection
#21
JOURNAL ARTICLE
Ariane Renita Lee, Kayla Roberta Wilson, Michele Clarke, Sven Engel, David C Tscharke, Thomas Gebhardt, Sammy Bedoui, Annabell Bachem
Naïve CD8+ T cells need to undergo a complex and coordinated differentiation program to gain the capacity to control virus infections. This not only involves the acquisition of effector functions, but also regulates the development of a subset of effector CD8+ T cells into long-lived and protective memory cells. Microbiota-derived metabolites have recently gained interest for their influence on T cells, but much remains unclear about their role in CD8+ T cell differentiation. In this study, we investigated the role of the G protein-coupled receptors (GPR)41 and GPR43 that can bind microbiota-derived short chain fatty acids (SCFAs) in CD8+ T cell priming following epicutaneous herpes simplex virus type 1 (HSV-1) infection...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38523150/fe-3-o-4-chitosan-zif-8-rvg29-an-anti-glioma-nanoplatform-guided-by-fixed-and-activated-by-alternating-magnetic-field
#22
JOURNAL ARTICLE
Mohammad-Nabil Savari
There is considerable interest in developing anti-glioma nanoplatforms. They make the all-in-one combination of therapies possible. Here we show how the selective Glioblastoma multiforme (GBM) cell killing of the here-established nanoplatforms increased after each coating and how the here-established vibration-inducing Alternating magnetic field (AMF) decreased the treatment time from 72 h to 30 s. Thanks to their magnetite core, these nanoplatforms can be guided to the tumor's specific site by a Fixed magnetic field, they bypass the Blood-Brain Barrier (BBB) and accumulate at the tumor site thanks to the RVG29 bonding to the G-protein on the ion-gated channel receptor known as the nicotinic acetylcholine receptor (nAchR), which expresses on BBB cells and overexpresses on GBM cells, and thanks to the positive charge gained by both chitosan and RVG29's peptide...
March 24, 2024: Scientific Reports
https://read.qxmd.com/read/38522808/deciphering-the-role-of-glycosaminoglycans-in-gpcr-signaling
#23
JOURNAL ARTICLE
Sofya Savransky, Alex D White, Jean-Pierre Vilardaga
G protein-coupled receptors (GPCR) and glycosaminoglycans (GAGs) are two essential components of the cell surface that regulate physiological processes in the body. GPCRs are the most extensive family of transmembrane receptors that control cellular responses to extracellular stimuli, while GAGs are polysaccharides that contribute to the function of the extracellular matrix (ECM). Due to their proximity to the plasma membrane, GAGs participate in signal transduction by interacting with various extracellular molecules and cell surface receptors...
March 22, 2024: Cellular Signalling
https://read.qxmd.com/read/38522762/blockade-of-endothelial-adenosine-receptor-2a-suppresses-atherosclerosis-in-vivo-through-inhibiting-creb-alk5-mediated-endothelial-to-mesenchymal-transition
#24
JOURNAL ARTICLE
Yongfeng Cai, Yaqi Zhou, Qiuhua Yang, Jiean Xu, Qingen Da, Qian Ma, Dingwei Zhao, Tammy Lu, Ha Won Kim, David Fulton, Xuejun Jiang, Neal L Weintraub, Kunzhe Dong, Suowen Xu, Mei Hong, Zhiping Liu, Yuqing Huo
Cardiovascular diseases (CVDs) are the leading cause of death worldwide, and morbidity and mortality rates continue to rise. Atherosclerosis constitutes the principal etiology of CVDs. Endothelial injury, inflammation, and dysfunction are the initiating factors of atherosclerosis. Recently, we reported that endothelial adenosine receptor 2A (ADORA2A), a G protein-coupled receptor (GPCR), plays critical roles in neovascularization disease and cerebrovascular disease. However, the precise role of endothelial ADORA2A in atherosclerosis is still not fully understood...
March 22, 2024: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/38522554/biochemical-pharmacology-of-adenylyl-cyclases-in-cancer
#25
REVIEW
Bikash Chandra Jena, Daniel P Flaherty, Valerie P O'Brien, Val J Watts
Globally, despite extensive research and pharmacological advancement, cancer remains one of the most common causes of mortality. Understanding the signaling pathways involved in cancer progression is essential for the discovery of new drug targets. The adenylyl cyclase (AC) superfamily comprises glycoproteins that regulate intracellular signaling and convert ATP into cyclic AMP, an important second messenger. The present review highlights the involvement of ACs in cancer progression and suppression broken down for each specific mammalian AC isoform...
March 22, 2024: Biochemical Pharmacology
https://read.qxmd.com/read/38522516/structural-determinants-of-the-direct-inhibition-of-girk-channels-by-sigma-1-receptor-antagonist
#26
JOURNAL ARTICLE
Chang Liu, I-Shan Chen, Michihiro Tateyama, Yoshihiro Kubo
G-protein-gated inward rectifier K+ (GIRK) channels play a critical role in the regulation of the excitability of cardiomyocytes and neurons and include GIRK1, GIRK2, GIRK3 and GIRK4 subfamily members. BD1047 dihydrobromide (BD1047) is one of the representative antagonists of multi-functional Sigma-1 receptor (S1R). In the analysis of the effect of BD1047 on the regulation of Gi-coupled receptors by S1R using GIRK channel as an effector, we observed that BD1047, as well as BD1063, directly inhibited GIRK currents even in the absence of S1R and in a voltage-independent manner...
March 22, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38522511/stabilization-of-interdomain-interactions-in-g-protein-%C3%AE-subunits-as-a-determinant-of-g%C3%AE-i-subtype-signaling-specificity
#27
JOURNAL ARTICLE
Tyler J Lefevre, Wenyuan Wei, Elizaveta Mukhaleva, Sai Pranathi Meda Venkata, Naincy R Chandan, Saji Abraham, Yong Li, Carmen W Dessauer, Nagarajan Vaidehi, Alan V Smrcka
Highly homologous members of the Gαi family, Gαi1-3 , have distinct tissue distributions and physiological functions, yet their biochemical and functional properties are very similar. We recently identified PDZ-RhoGEF (PRG) as a novel Gαi1 effector that is poorly activated by Gαi2 . In a proteomic proximity labeling screen we observed a strong preference for Gαi1 relative to Gαi2 with respect to engagement of a broad range of potential targets. We investigated the mechanistic basis for this selectivity using PRG as a representative target...
March 22, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38521930/human-derived-bacterial-strains-mitigate-colitis-via-modulating-gut-microbiota-and-repairing-intestinal-barrier-function-in-mice
#28
JOURNAL ARTICLE
Juanjuan Dai, Mingjie Jiang, Xiaoxin Wang, Tao Lang, Leilei Wan, Jingjing Wang
BACKGROUND: Unbalanced gut microbiota is considered as a pivotal etiological factor in colitis. Nevertheless, the precise influence of the endogenous gut microbiota composition on the therapeutic efficacy of probiotics in colitis remains largely unexplored. RESULTS: In this study, we isolated bacteria from fecal samples of a healthy donor and a patient with ulcerative colitis in remission. Subsequently, we identified three bacterial strains that exhibited a notable ability to ameliorate dextran sulfate sodium (DSS)-induced colitis, as evidenced by increased colon length, reduced disease activity index, and improved histological score...
March 23, 2024: BMC Microbiology
https://read.qxmd.com/read/38521467/camp-in-budding-yeast-also-a-messenger-for-sucrose-metabolism
#29
JOURNAL ARTICLE
Dennis Botman, Sineka Kanagasabapathi, Mila I Rep, Kelly van Rossum, Evelina Tutucci, Bas Teusink
S. cerevisiae (or budding yeast) is an important micro-organism for sucrose-based fermentation in biotechnology. Yet, it is largely unknown how budding yeast adapts to sucrose transitions. Sucrose can only be metabolized when the invertase or the maltose machinery are expressed and we propose that the Gpr1p receptor signals extracellular sucrose availability via the cAMP peak to adapt cells accordingly. A transition to sucrose or glucose gave a transient cAMP peak which was maximally induced for sucrose. When transitioned to sucrose, cAMP signalling mutants showed an impaired cAMP peak together with a lower growth rate, a longer lag phase and a higher final OD600 compared to a glucose transition...
March 21, 2024: Biochimica et Biophysica Acta. Molecular Cell Research
https://read.qxmd.com/read/38521431/qixian-granule-inhibits-ferroptosis-in-vascular-endothelial-cells-by-modulating-trpml1-in-the-lysosome-to-prevent-postmenopausal-atherosclerosis
#30
JOURNAL ARTICLE
Meng Zhang, Chenhan Mao, Yang Dai, Xiaojin Xu, Xindong Wang
ETHNOPHARMACOLOGICAL RELEVANCE: QiXian Granule (QXG) is an integrated traditional Chinese medicine formula used to treat postmenopausal atherosclerotic (AS) cardiovascular diseases. The previous studies have found that QXG inhibited isoproterenol (ISO)-induced myocardial remodeling. And its active ingredient, Icraiin, can inhibit ferroptosis by promoting oxidized low-density lipoprotein (xo-LDL)-induced vascular endothelial cell injury and autophagy in atherosclerotic mice. Another active ingredient, Salvianolic Acid B, can suppress ferroptosis and apoptosis during myocardial ischemia/reperfusion injury by reducing ubiquitin-proteasome degradation of Glutathione Peroxidase 4 (GPX4) and down-regulating the reactive oxygen species (ROS)- c-Jun N-terminal kinases (JNK)/mitogen-activated protein kinase (MAPK) pathway...
March 21, 2024: Journal of Ethnopharmacology
https://read.qxmd.com/read/38519141/cxcr4-from-b-cell-development-to-b-cell-mediated-diseases
#31
REVIEW
Stéphane Giorgiutti, Julien Rottura, Anne-Sophie Korganow, Vincent Gies
Chemokine receptors are members of the G protein-coupled receptor superfamily. The C-X-C chemokine receptor type 4 (CXCR4), one of the most studied chemokine receptors, is widely expressed in hematopoietic and immune cell populations. It is involved in leukocyte trafficking in lymphoid organs and inflammatory sites through its interaction with its natural ligand CXCL12. CXCR4 assumes a pivotal role in B-cell development, ranging from early progenitors to the differentiation of antibody-secreting cells. This review emphasizes the significance of CXCR4 across the various stages of B-cell development, including central tolerance, and delves into the association between CXCR4 and B cell-mediated disorders, from immunodeficiencies such as WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome to autoimmune diseases such as systemic lupus erythematosus...
June 2024: Life Science Alliance
https://read.qxmd.com/read/38517694/gpcr-ipl-score-multilevel-featurization-of-gpcr-ligand-interaction-patterns-and-prediction-of-ligand-functions-from-selectivity-to-biased-activation
#32
JOURNAL ARTICLE
Surendra Kumar, Mahesh K Teli, Mi-Hyun Kim
G-protein-coupled receptors (GPCRs) mediate diverse cell signaling cascades after recognizing extracellular ligands. Despite the successful history of known GPCR drugs, a lack of mechanistic insight into GPCR challenges both the deorphanization of some GPCRs and optimization of the structure-activity relationship of their ligands. Notably, replacing a small substituent on a GPCR ligand can significantly alter extracellular GPCR-ligand interaction patterns and motion of transmembrane helices in turn to occur post-binding events of the ligand...
January 22, 2024: Briefings in Bioinformatics
https://read.qxmd.com/read/38517202/microbially-conjugated-bile-salts-found-in-human-bile-activate-the-bile-salt-receptors-tgr5-and-fxr
#33
JOURNAL ARTICLE
Ümran Ay, Martin Leníček, Raphael S Haider, Arno Classen, Hans van Eijk, Kiran V K Koelfat, Gregory van der Kroft, Ulf P Neumann, Carsten Hoffmann, Carsten Bolm, Steven W M Olde Damink, Frank G Schaap
BACKGROUND: Bile salts of hepatic and microbial origin mediate interorgan cross talk in the gut-liver axis. Here, we assessed whether the newly discovered class of microbial bile salt conjugates (MBSCs) activate the main host bile salt receptors (Takeda G protein-coupled receptor 5 [TGR5] and farnesoid X receptor [FXR]) and enter the human systemic and enterohepatic circulation. METHODS: N-amidates of (chenodeoxy) cholic acid and leucine, tyrosine, and phenylalanine were synthesized...
April 1, 2024: Hepatology Communications
https://read.qxmd.com/read/38516403/infrared-multiphoton-dissociation-enables-top-down-characterization-of-membrane-protein-complexes-and-g-protein-coupled-receptors
#34
JOURNAL ARTICLE
Corinne A Lutomski, Tarick J El-Baba, Joshua D Hinkle, Idlir Liko, Jack L Bennett, Neha V Kalmankar, Andrew Dolan, Carla Kirschbaum, Kim Greis, Leonhard H Urner, Parth Kapoor, Hsin-Yung Yen, Kevin Pagel, Christopher Mullen, John E P Syka, Carol V Robinson
Membrane proteins are challenging to analyze by native mass spectrometry (MS) as their hydrophobic nature typically requires stabilization in detergent micelles that are removed prior to analysis via collisional activation. There is however a practical limit to the amount of energy which can be applied, which often precludes subsequent characterization by top-down MS. To overcome this barrier, we have applied a modified Orbitrap Eclipse Tribrid mass spectrometer coupled to an infrared laser within a high-pressure linear ion trap...
September 4, 2023: Angewandte Chemie
https://read.qxmd.com/read/38516305/acid-resistant-bodipy-amino-acids-for-peptide-based-fluorescence-imaging-of-gpr54-receptors-in-pancreatic-islets
#35
JOURNAL ARTICLE
Lorena Mendive-Tapia, Laia Miret-Casals, Nicole D Barth, Jinling Wang, Anne de Bray, Massimiliano Beltramo, Vincent Robert, Christophe Ampe, David J Hodson, Annemieke Madder, Marc Vendrell
The G protein-coupled kisspeptin receptor (GPR54 or KISS1R) is an important mediator in reproduction, metabolism and cancer biology; however, there are limited fluorescent probes or antibodies for direct imaging of these receptors in cells and intact tissues, which can help to interrogate their multiple biological roles. Herein, we describe the rational design and characterization of a new acid-resistant BODIPY-based amino acid (Trp-BODIPY PLUS), and its implementation for solid-phase synthesis of fluorescent bioactive peptides...
May 8, 2023: Angewandte Chemie
https://read.qxmd.com/read/38515458/validation-of-cdc45-as-a-novel-biomarker-for-diagnosis-and-prognosis-of-gastric-cancer
#36
JOURNAL ARTICLE
Lihua Wu, Gan Gao, Hui Mi, Zhou Luo, Zheng Wang, Yongdong Liu, Liangyan Wu, Haihua Long, Yongqi Shen
BACKGROUND: Cell division cycle protein 45 (CDC45) has been demonstrated to play vital roles in the progression of various malignancies. However, the clinical significance of CDC45 in gastric cancer (GC) remains unreported. METHOD: In this study, we employed the TCGA database and the TCGA & GTEx dataset to compare the mRNA expression levels of CDC45 between gastric cancer tissues and adjacent or normal tissues ( p < 0.05 was considered statistically significant), which was further validated in multiple datasets including GSE13911, GSE29272, GSE118916, GSE66229, as well as RT-qPCR...
2024: PeerJ
https://read.qxmd.com/read/38515135/recent-research-advances-in-pain-mechanisms-in-mccune-albright-syndrome-thinking-about-the-pain-mechanism-of-fd-mas
#37
REVIEW
Yong Wang, Tao Jiang
BACKGROUND: The lack of effective understanding of the pain mechanism of McCune-Albright syndrome (MAS) has made the treatment of pain in this disease a difficult clinical challenge, and new therapeutic targets are urgently needed to address this dilemma. OBJECTIVE: This paper summarizes the novel mechanisms, targets, and treatments that may produce pain in MAS and fibrous dysplasia (polyfibrous dysplasia, or FD). METHODS: We conducted a systematic search in the PubMed database, Web of Science, China Knowledge Network (CNKI) with the following keywords: "McCune-Albright syndrome (MAS); polyfibrous dysplasia (FD); bone pain; bone remodeling; G protein coupled receptors; GDNF family receptors; purinergic receptors and glycogen synthase kinase", as well as other keywords were systematically searched...
March 21, 2024: Journal of Orthopaedic Surgery and Research
https://read.qxmd.com/read/38514862/gpr41-deficiency-aggravates-type-1-diabetes-in-streptozotocin-treated-mice-by-promoting-dendritic-cell-maturation
#38
JOURNAL ARTICLE
Jia-Hong Li, Ming Zhang, Zhao-di Zhang, Xiao-Hua Pan, Li-Long Pan, Jia Sun
Disturbances in intestinal immune homeostasis predispose susceptible individuals to type 1 diabetes (T1D). G-protein-coupled receptor 41 (GPR41) is a receptor for short-chain fatty acids (SCFAs) mainly produced by gut microbiota, which plays key roles in maintaining intestinal homeostasis. In this study, we investigated the role of GPR41 in the progression of T1D. In non-obese diabetic (NOD) mice, we found that aberrant reduction of GPR41 expression in the pancreas and colons was associated with the development of T1D...
March 21, 2024: Acta Pharmacologica Sinica
https://read.qxmd.com/read/38514778/a-multicolor-suite-for-deciphering-population-coding-of-calcium-and-camp-in-vivo
#39
JOURNAL ARTICLE
Tatsushi Yokoyama, Satoshi Manita, Hiroyuki Uwamori, Mio Tajiri, Itaru Imayoshi, Sho Yagishita, Masanori Murayama, Kazuo Kitamura, Masayuki Sakamoto
cAMP is a universal second messenger regulated by various upstream pathways including Ca2+ and G-protein-coupled receptors (GPCRs). To decipher in vivo cAMP dynamics, we rationally designed cAMPinG1, a sensitive genetically encoded green cAMP indicator that outperformed its predecessors in both dynamic range and cAMP affinity. Two-photon cAMPinG1 imaging detected cAMP transients in the somata and dendritic spines of neurons in the mouse visual cortex on the order of tens of seconds. In addition, multicolor imaging with a sensitive red Ca2+ indicator RCaMP3 allowed simultaneous measurement of population patterns in Ca2+ and cAMP in hundreds of neurons...
March 21, 2024: Nature Methods
https://read.qxmd.com/read/38514730/bile-acid-metabolites-enhance-expression-of-cathelicidin-antimicrobial-peptide-in-airway-epithelium-through-activation-of-the-tgr5-erk1-2-pathway
#40
JOURNAL ARTICLE
Iwona T Myszor, Kornelia Lapka, Kristjan Hermannsson, Rokeya Sultana Rekha, Peter Bergman, Gudmundur Hrafn Gudmundsson
Signals for the maintenance of epithelial homeostasis are provided in part by commensal bacteria metabolites, that promote tissue homeostasis in the gut and remote organs as microbiota metabolites enter the bloodstream. In our study, we investigated the effects of bile acid metabolites, 3-oxolithocholic acid (3-oxoLCA), alloisolithocholic acid (AILCA) and isolithocholic acid (ILCA) produced from lithocholic acid (LCA) by microbiota, on the regulation of innate immune responses connected to the expression of host defense peptide cathelicidin in lung epithelial cells...
March 21, 2024: Scientific Reports
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