Cytostatic Activity and Ligand-Receptor Interaction Energy of the Novel Russian-Produced Gestagen Gestobutanoil and its Metabolites

2021 ◽  
Vol 54 (11) ◽  
pp. 1087-1092
Author(s):  
A. V. Semeikin ◽  
T. A. Fedotcheva ◽  
E. D. Sveshnikova ◽  
B. V. Shilov ◽  
A. S. Smirnov ◽  
...  
Keyword(s):  
Interaction Energy ◽  
Cytostatic Activity ◽  
Receptor Interaction ◽  
The Novel

scholarly journals Identification of Differentially Expressed Genes in Porcine Ovaries at Proestrus and Estrus Stages Using RNA-Seq Technique

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Songbai Yang ◽  
Xiaolong Zhou ◽  
Yue Pei ◽  
Han Wang ◽  
Ke He ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Hormone Secretion ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
The Novel ◽  
Kegg Pathways ◽  
Go Enrichment ◽  
Single Organism

Estrus is an important factor for the fecundity of sows, and it is involved in ovulation and hormone secretion in ovaries. To better understand the molecular mechanisms of porcine estrus, the expression patterns of ovarian mRNA at proestrus and estrus stages were analyzed using RNA sequencing technology. A total of 2,167 differentially expressed genes (DEGs) were identified (P≤0.05, log2  Ratio≥1), of which 784 were upregulated and 1,383 were downregulated in the estrus compared with the proestrus group. Gene Ontology (GO) enrichment indicated that these DEGs were mainly involved in the cellular process, single-organism process, cell and cell part, and binding and metabolic process. In addition, a pathway analysis showed that these DEGs were significantly enriched in 33 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including cell adhesion molecules, ECM-receptor interaction, and cytokine-cytokine receptor interaction. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) confirmed the differential expression of 10 selected DEGs. Many of the novel candidate genes identified in this study will be valuable for understanding the molecular mechanisms of the sow estrous cycle.

scholarly journals Rescue of a pathogenic mutant human glucagon receptor by pharmacological chaperones

2012 ◽  
Vol 49 (2) ◽  
pp. 69-78 ◽  
Author(s):  
Run Yu ◽  
Chun-Rong Chen ◽  
Xiaohong Liu ◽  
János T Kodra
Keyword(s):  
Plasma Membrane ◽  
Fluorescent Protein ◽  
Receptor Interaction ◽  
The Novel ◽  
Camp Production ◽  
Cell Hyperplasia ◽  
Glucagon Receptor ◽  
Hek 293 ◽  
Pharmacological Chaperones ◽  
Green Fluorescent

We have previously demonstrated that a homozygous inactivating P86S mutation of the glucagon receptor (GCGR) causes a novel human disease of hyperglucagonemia, pancreatic α-cell hyperplasia, and pancreatic neuroendocrine tumors (Mahvash disease). The mechanisms for the decreased activity of the P86S mutant (P86S) are abnormal receptor localization to the endoplasmic reticulum (ER) and defective interaction with glucagon. To search for targeted therapies for Mahvash disease, we examined whether P86S can be trafficked to the plasma membrane by pharmacological chaperones and whether novel glucagon analogs restore effective receptor interaction. We used enhanced green fluorescent protein-tagged P86S stably expressed in HEK 293 cells to allow fluorescence imaging and western blotting and molecular modeling to design novel glucagon analogs in which alanine 19 was replaced with serine or asparagine. Incubation at 27 °C largely restored normal plasma membrane localization and normal processing of P86S but osmotic chaperones had no effects. The ER stressors thapsigargin and curcumin partially rescued P86S. The lipophilic GCGR antagonist L-168,049 also partially rescued P86S, so did Cpd 13 and 15 to a smaller degree. The rescued P86S led to more glucagon-stimulated cAMP production and was internalized by glucagon. Compared with the native glucagon, the novel glucagon analogs failed to stimulate more cAMP production by P86S. We conclude that the mutant GCGR is partially rescued by several pharmacological chaperones and our data provide proof-of-principle evidence that Mahvash disease can be potentially treated with pharmacological chaperones. The novel glucagon analogs, however, failed to interact with P86S more effectively.

scholarly journals Coevolution of the Spexin/Galanin/Kisspeptin Family: Spexin Activates Galanin Receptor Type II and III

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1864-1873 ◽  
Author(s):  
Dong-Kyu Kim ◽  
Seongsik Yun ◽  
Gi Hoon Son ◽  
Jong-Ik Hwang ◽  
Cho Rong Park ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
Evolutionary Relationship ◽  
G Protein Coupled Receptors ◽  
Receptor Interaction ◽  
The Novel ◽  
Natural Ligands ◽  
Peptide Gene ◽  
Relationship Of ◽  
G Protein Coupled ◽  
Syntenic Analysis

The novel neuropeptide spexin (SPX) was discovered using bioinformatics. The function of this peptide is currently under investigation. Here, we identified SPX along with a second SPX gene (SPX2) in vertebrate genomes. Syntenic analysis and relocating SPXs and their neighbor genes on reconstructed vertebrate ancestral chromosomes revealed that SPXs reside in the near vicinity of the kisspeptin (KISS) and galanin (GAL) family genes on the chromosomes. Alignment of mature peptide sequences showed some extent of sequence similarity among the 3 peptide groups. Gene structure analysis indicated that SPX is more closely related to GAL than KISS. These results suggest that the SPX, GAL, and KISS genes arose through local duplications before 2 rounds (2R) of whole-genome duplication. Receptors of KISS and GAL (GAL receptor [GALR]) are phylogenetically closest among rhodopsin-like G protein-coupled receptors, and synteny revealed the presence of 3 distinct receptor families KISS receptor, GALR1, and GALR2/3 before 2R. A ligand-receptor interaction study showed that SPXs activate human, Xenopus, and zebrafish GALR2/3 family receptors but not GALR1, suggesting that SPXs are natural ligands for GALR2/3. Particularly, SPXs exhibited much higher potency toward GALR3 than GAL. Together, these results identify the coevolution of SPX/GAL/KISS ligand genes with their receptor genes. This study demonstrates the advantage of evolutionary genomics to explore the evolutionary relationship of a peptide gene family that arose before 2R by local duplications.

Synthesis, structure and in vitro cytostatic activity study of the novel organotin(IV) derivatives of p -aminobenzenesulfonic acid

2018 ◽  
Vol 861 ◽  
pp. 151-158 ◽  
Author(s):  
Ge-Hua Wen ◽  
Ru-Fen Zhang ◽  
Qian-Li Li ◽  
Shao-Liang Zhang ◽  
Jing Ru ◽  
...  
Keyword(s):  
Cytostatic Activity ◽  
The Novel ◽  
Derivatives Of

The novel coumarin[3,2-c]thiophene and its hydroxamic acid and ureido derivatives: synthesis and cytostatic activity evaluations

2016 ◽  
Vol 25 (4) ◽  
pp. 728-737 ◽  
Author(s):  
Karlo Wittine ◽  
Ivana Ratkaj ◽  
Krešimir Benci ◽  
Tomislav Suhina ◽  
Leo Mandić ◽  
...  
Keyword(s):  
Hydroxamic Acid ◽  
Cytostatic Activity ◽  
The Novel

scholarly journals Allosteric Receptor Modulation uncovers an FFAR2 antagonist as a positive orthosteric modulator/agonist in disguise

2021 ◽  
Author(s):  
Simon Lind ◽  
Dagny Olofsson Hoffman ◽  
Huamei Forsman ◽  
Claes Dahlgren
Keyword(s):  
Nadph Oxidase ◽  
Inhibitory Effect ◽  
Receptor Interaction ◽  
Free Calcium ◽  
The Novel ◽  
Receptor Modulation ◽  
Biased Signaling ◽  
Positive Modulator ◽  
Receptor Cross Talk ◽  
Modulating Functions

Two earlier described Free Fatty Acid Receptor 2 (FFAR2)-specific antagonists (CATPB and GLPG0974) have different receptor-interaction characteristics at the molecular/functional level. The inhibitory effect of the two antagonists, on the novel receptor-cross-talk activation signals generated by the ATP-receptor, show that both antagonists inhibit the effect of the positive allosteric FFAR2 modulators (PAMs) AZ1729 and Cmp58. No neutrophil activation was induced by AZ1729 or Cmp58 alone, but together they were co-agonistic PAMs and activated the superoxide generating NADPH-oxidase in neutrophils. This response was inhibited by CATPB but not by GLPG0974; in contrast, GLPG0974 acted as a positive modulator that increased the potency but not the efficacy of the response. At the signaling level, GLPG0974 changed the biased signaling induced by the co-agonistic PAMs, to include a rise in the cytosolic concentration of free calcium ions (Ca2+). This effect was reciprocal, i.e., GLPG0974 triggers a rise in intracellular Ca2+, demonstrating that GLPG0974 may act as an FFAR2 agonist. In summary, by studying the effects of the FFAR2 ligand GLPG0974 on neutrophils activation induced by the co-agonists AZ1729 and Cmp58, we reveal that GLPG0974 in addition to be an antagonist, displays also agonistic and positive FFAR2 modulating functions that affects the NADPH-oxidase activity and the receptor down-stream signaling induced by the two co-agonistic PAMs.

scholarly journals The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs

2016 ◽  
Vol 2 (8) ◽  
pp. e1501929 ◽  
Author(s):  
Hyunwook Lee ◽  
Kristin L. Shingler ◽  
Lindsey J. Organtini ◽  
Robert E. Ashley ◽  
Alexander M. Makhov ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Conformational Changes ◽  
Viral Proteins ◽  
Receptor Interaction ◽  
Icosahedral Symmetry ◽  
The Novel ◽  
Structural Studies ◽  
Cryo Electron Microscopy ◽  
Unique Site

Many nonenveloped viruses engage host receptors that initiate capsid conformational changes necessary for genome release. Structural studies on the mechanisms of picornavirus entry have relied on in vitro approaches of virus incubated at high temperatures or with excess receptor molecules to trigger the entry intermediate or A-particle. We have induced the coxsackievirus B3 entry intermediate by triggering the virus with full-length receptors embedded in lipid bilayer nanodiscs. These asymmetrically formed A-particles were reconstructed using cryo-electron microscopy and a direct electron detector. These first high-resolution structures of a picornavirus entry intermediate captured at a membrane with and without imposing icosahedral symmetry (3.9 and 7.8 Å, respectively) revealed a novel A-particle that is markedly different from the classical A-particles. The asymmetric receptor binding triggers minimal global capsid expansion but marked local conformational changes at the site of receptor interaction. In addition, viral proteins extrude from the capsid only at the site of extensive protein remodeling adjacent to the nanodisc. Thus, the binding of the receptor triggers formation of a unique site in preparation for genome release.

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