keyword
https://read.qxmd.com/read/38522516/structural-determinants-of-the-direct-inhibition-of-girk-channels-by-sigma-1-receptor-antagonist
#21
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
#22
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
#23
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
#24
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
#25
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
#26
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
#27
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
#28
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
#29
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
#30
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
#31
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
#32
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
#33
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
#34
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
#35
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
https://read.qxmd.com/read/38514581/role-of-ph-sensing-receptors-in-colitis
#36
REVIEW
Martin Hausmann, Klaus Seuwen, Cheryl de Vallière, Moana Busch, Pedro A Ruiz, Gerhard Rogler
Low pH in the gut is associated with severe inflammation, fibrosis, and colorectal cancer (CRC) and is a hallmark of active inflammatory bowel disease (IBD). Subsequently, pH-sensing mechanisms are of interest for the understanding of IBD pathophysiology. Tissue hypoxia and acidosis-two contributing factors to disease pathophysiology-are linked to IBD, and understanding their interplay is highly relevant for the development of new therapeutic options. One member of the proton-sensing G protein-coupled receptor (GPCR) family, GPR65 (T-cell death-associated gene 8, TDAG8), was identified as a susceptibility gene for IBD in a large genome-wide association study...
March 22, 2024: Pflügers Archiv: European Journal of Physiology
https://read.qxmd.com/read/38514486/knockout-of-lws1-in-zebrafish-danio-rerio-reveals-its-role-in-regulating-feeding-and-vision-guided-behavior
#37
JOURNAL ARTICLE
Di-Mei Xu, Fa-Rui Chai, Xu-Fang Liang, Ke Lu
Long-wave sensitive (LWS) is a G protein-coupled receptor expressed in the retina, and zebrafish is a better model organism for studying vision, but the role of LWS1 in vision-guided behavior of larvae fish has rarely been reported. In this study, we found that zebrafish lws1 and lws2 are tandemly replicated genes, both with six exons, with lws1 being more evolutionarily conserved. The presence of Y277F in the amino acid sequence of lws2 may have contributed to the shift of λmax to green light. We established a lws1 knockout zebrafish model using CRISPR/Cas9 technology...
March 22, 2024: Functional & Integrative Genomics
https://read.qxmd.com/read/38514303/from-orphan-to-oncogene-the-role-of-gpr35-in-cancer-and-immune-modulation
#38
REVIEW
Simran Takkar, Gunjan Sharma, Jyoti B Kaushal, K M Abdullah, Surinder K Batra, Jawed A Siddiqui
G protein-coupled receptors (GPCRs) are well-studied and the most traceable cell surface receptors for drug discovery. One of the intriguing members of this family is G protein-coupled receptors 35 (GPR35), which belongs to the class A rhodopsin-like family of GPCRs identified over two decades ago. GPR35 presents interesting features such as ubiquitous expression and distinct isoforms. Moreover, functional and genome-wide association studies on its widespread expression have linked GPR35 with pathophysiological disease progression...
March 19, 2024: Cytokine & Growth Factor Reviews
https://read.qxmd.com/read/38513777/elucidation-of-active-components-and-target-mechanism-in-jinqiancao-granules-for-the-treatment-of-prostatitis-and-benign-prostatic-hyperplasia
#39
JOURNAL ARTICLE
Han Zhou, Tao Hou, Aijin Shen, Wenyi Yu, Liangliang Zhou, Wenjie Yuan, Wanxian Wang, Yumin Yao, Jixia Wang, Yanfang Liu, Xinmiao Liang
ETHNOPHARMACOLOGICAL RELEVANCE: Prostatitis and benign prostatic hyperplasia (BPH) are inflammations of the prostate gland, which surrounds the urethra in males. Jinqiancao granules are a traditional Chinese medicine used to treat kidney stones and this medicine consists of four herbs: Desmodium styracifolium (Osbeck) Merr., Pyrrosia calvata (Baker) Ching, Plantago asiatica L. and stigma of Zea mays L. AIM OF THE STUDY: We hypothesized that Jinqiancao granules could be a potential therapy for prostatitis and BPH, and this work aimed to elucidate active compounds in Jinqiancao granules and their target mechanisms for the potential treatment of the two diseases...
March 19, 2024: Journal of Ethnopharmacology
https://read.qxmd.com/read/38512659/interaction-of-tau-with-g-protein-coupled-purinergic-p2y12-receptor-by-molecular-docking-and-molecular-dynamic-simulation
#40
JOURNAL ARTICLE
Hariharakrishnan Chidambaram, Smita Eknath Desale, Subashchandrabose Chinnathambi
Alzheimer's disease, a progressive neurological disorder, is characterized by the accumulation of neurofibrillary tangles and senile plaques by Tau and amyloid-β, respectively, in the brain microenvironment. The misfolded protein aggregates interact with several components of neuronal and glial cells such as membrane lipids, receptors, transporters, enzymes, cytoskeletal proteins, etc. Under pathological conditions, Tau interacts with several G-protein-coupled receptors (GPCRs), which undergoes either receptor signaling or desensitization followed by internalization of the protein complex...
2024: Methods in Molecular Biology
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