Some taste substances are direct activators of G-proteins.
Ontology highlight
ABSTRACT:
SUBMITTER: Naim M
PROVIDER: S-EPMC1137854 | biostudies-other | 1994 Feb
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Although FoxO and Pax proteins represent two important families of transcription factors in determining cell fate, they had not been functionally or physically linked together in mediating regulation of a common target gene during normal cellular transcription programs. Here, we identify MyoD, a key regulator of myogenesis, as a direct target of FoxO3 and Pax3/7 in myoblasts. Our cell-based assays and in vitro studies reveal a tight codependent partnership between FoxO3 and Pax3/7 to coordinately recruit RNA polymerase II and form a preinitiation complex (PIC) to activate MyoD transcription in myoblasts. The role of FoxO3 in regulating muscle differentiation is confirmed in vivo by observed defects in muscle regeneration caused by MyoD downregulation in FoxO3 null mice. These data establish a mutual interdependence and functional link between two families of transcription activators serving as potential signaling sensors and regulators of cell fate commitment in directing tissue specific MyoD transcription.
| S-EPMC2614327 | biostudies-literature
Project description:AMP-activated protein kinase (AMPK) is an evolutionarily conserved fuel-sensing enzyme that is activated in shortage of energy and suppressed in its surfeit. AMPK activation stimulates fatty acid oxidation, enhances insulin sensitivity, alleviates hyperglycemia and hyperlipidemia, and inhibits proinflammatory changes. Thus, AMPK is a well-received therapeutic target for type 2 diabetes and other metabolic disorders. Here, we will report the discovery of pyrrolopyridone derivatives as AMPK direct activators. We will illustrate the synthesis and structure-activity relationships of the series as well as some pharmacokinetic results. Some compounds exhibited encouraging oral exposure and were evaluated in a mouse diabetic model. Compound 17 showed oral activity at 30 mg/kg on blood glucose.
| S-EPMC4027520 | biostudies-literature
Project description:The taste receptor type 1 (T1r) family perceives 'palatable' tastes. These receptors function as T1r2-T1r3 and T1r1-T1r3 heterodimers to recognize a wide array of sweet and umami (savory) tastes in sugars and amino acids. Nonetheless, it is unclear how diverse tastes are recognized by so few receptors. Here we present crystal structures of the extracellular ligand-binding domains (LBDs), the taste recognition regions of the fish T1r2-T1r3 heterodimer, bound to different amino acids. The ligand-binding pocket in T1r2LBD is rich in aromatic residues, spacious and accommodates hydrated percepts. Biophysical studies show that this binding site is characterized by a broad yet discriminating chemical recognition, contributing for the particular trait of taste perception. In contrast, the analogous pocket in T1r3LBD is occupied by a rather loosely bound amino acid, suggesting that the T1r3 has an auxiliary role. Overall, we provide a structural basis for understanding the chemical perception of taste receptors.
| S-EPMC5457512 | biostudies-literature
Project description:Taste stimuli are normally dissolved in saliva prior to interacting with their respective receptor targets. There are hundreds of proteins in saliva, and it has been hypothesized that these proteins could interact with either taste stimuli or taste receptors to alter taste signaling and diet acceptance. However, the impact of these proteins on feeding has been relatively unexplored using rodent models. We have developed a novel technique for saliva collection that allows us to link salivary protein expression with feeding behavior. First, we monitored the microstructure of rats' feeding patterns on a 0.375% quinine diet (Q-diet) while tracking changes in salivary protein expression. We found 5 protein bands were upregulated by diet exposure to Q-diet and upregulation of a subset of these bands were statistically related to increased diet acceptance, including changes in behavioral measures that are thought to represent both orosensory and postingestive signaling. In a second experiment, we measured the licking to a range of quinine solutions (0.01-1.0mM) before and after the animals were exposed to a tannic acid diet that altered salivary protein expression. Rats found the quinine solutions less aversive after salivary protein altering diets. In a third experiment we recorded the response of the chorda tympani (CT) nerve while delivering quinine solutions (0.3-30mM) to the front of the tongue dissolved in either "donor saliva" containing salivary proteins or donor saliva which has had the salivary proteins removed. Donor saliva was collected from a separate group of animals using isoproterenol and pilocarpine. The samples containing salivary proteins resulted in lower nerve responses than those without salivary proteins. Together these data suggest that salivary proteins are capable of altering taste-guided behaviors and taste nerve signaling.
| S-EPMC5749268 | biostudies-literature
Project description:Recently, we reported that calcium-sensing receptor (CaSR) is a receptor for kokumi substances, which enhance the intensities of salty, sweet and umami tastes. Furthermore, we found that several γ-glutamyl peptides, which are CaSR agonists, are kokumi substances. In this study, we elucidated the receptor cells for kokumi substances, and their physiological properties. For this purpose, we used Calcium Green-1 loaded mouse taste cells in lingual tissue slices and confocal microscopy. Kokumi substances, applied focally around taste pores, induced an increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in a subset of taste cells. These responses were inhibited by pretreatment with the CaSR inhibitor, NPS2143. However, the kokumi substance-induced responses did not require extracellular Ca(2+). CaSR-expressing taste cells are a different subset of cells from the T1R3-expressing umami or sweet taste receptor cells. These observations indicate that CaSR-expressing taste cells are the primary detectors of kokumi substances, and that they are an independent population from the influenced basic taste receptor cells, at least in the case of sweet and umami.
| S-EPMC3325276 | biostudies-literature
Project description:The constitutive androstane receptor (CAR; NR1I3) is a member of the nuclear receptor superfamily and functions as an important xenochemical sensor and transcriptional modulator in mammalian cells. Upon chemical activation, CAR undergoes nuclear translocation and heterodimerization with the retinoid X receptor subsequent to its DNA target interaction. CAR is unusual among nuclear receptors in that it possesses a high level of constitutive activity in cell-based assays, obscuring the detection of ligand activators. However, a human splice variant of CAR, termed CAR3, exhibits negligible constitutive activity. In addition, CAR3 is activated by ligands with similar specificity as the reference form of the receptor. In this study, we hypothesized that similar CAR3 receptors could be constructed across various mammalian species' forms of CAR that would preserve species-specific ligand responses, thus enabling a more sensitive and differential screening assessment of CAR response among animal models. A battery of CAR3 receptors was produced in mouse, rat, and dog and comparatively evaluated with selected ligands together with human CAR1 and CAR3 in mammalian cell reporter assays. The results demonstrate that the 5-amino acid insertion that typifies human CAR3 also imparts ligand-activated receptor function in other species' CAR while maintaining signature responses in each species to select CAR ligands. These variant constructs permit in vitro evaluation of differential chemical effector responses across species and coupled with in vivo assays, the species-selective contributions of CAR in normal physiology and in disease processes such as hepatocarcinogenesis.
| S-EPMC3179682 | biostudies-literature
Project description:The flavor and quality of tea largely depends on the cultivar from which it is processed; however, the cultivar effect on the taste and aroma characteristics of Hakka stir-fried green tea (HSGT) has received little attention. High-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and sensory evaluations were used to detect and predict the essential taste and aroma-contributing substances of HSGTs made from Huangdan (HD), Meizhan (MZ) and Qingliang Mountain (QL) cultivars. Orthogonal partial least squares data analysis (OPLS-DA) ranked four substances that putatively distinguished the tastes of the HSGTs, epigallocatechin gallate (EGCG) > theanine > epigallocatechin (EGC) > epicatechin gallate (ECG). Ten substances with variable importance in projections (VIPs) ≥ 1 and odor activation values (OAVs) ≥ 1 contributed to their overall aromas, with geranylacetone having the most significant effect on HD (OAV 1841), MZ (OAV 4402), and QL (OAV 1211). Additionally, sensory evaluations found that HD was relatively equivalent to QL in quality, and both were superior to MZ. HD had a distinct floral aroma, MZ had a distinct fried rice aroma, and QL had a balance of fried rice and fresh aromas. The results provide a theoretical framework for evaluating the cultivar effect on the quality of HSGT and put forward ideas for future HSGT cultivar development.
| S-EPMC10217579 | biostudies-literature
Project description:In Escherichia coli , the bifunctional penicillin-binding proteins (PBPs), PBP1A and PBP1B, play critical roles in the final stage of peptidoglycan (PG) biosynthesis. These synthetic enzymes each possess a PG glycosyltransferase (PGT) domain and a transpeptidase (TP) domain. Recent genetic experiments have shown that PBP1A and PBP1B each require an outer membrane lipoprotein, LpoA and LpoB, respectively, to function properly in vivo. Here, we use complementary assays to show that LpoA and LpoB each increase the PGT and TP activities of their cognate PBPs, albeit by different mechanisms. LpoA directly increases the rate of the PBP1A TP reaction, which also results in enhanced PGT activity; in contrast, LpoB directly affects PGT domain activity, resulting in enhanced TP activity. These studies demonstrate bidirectional coupling of PGT and TP domain function. Additionally, the transpeptidation assay described here can be applied to study other activators or inhibitors of the TP domain of PBPs, which are validated drug targets.
| S-EPMC3961711 | biostudies-literature
Project description:The CREB regulated transcription co-activators (CRTCs) regulate many biological processes by integrating and converting environmental inputs into transcriptional responses. Although the mechanisms by which CRTCs sense cellular signals are characterized, little is known regarding how CRTCs contribute to the regulation of cAMP inducible genes. Here we show that these dynamic regulators, unlike other co-activators, independently direct either pre-mRNA splice-site selection or transcriptional activation depending on the cell type or promoter context. Moreover, in other scenarios, the CRTC co-activators coordinately regulate transcription and splicing. Mutational analyses showed that CRTCs possess distinct functional domains responsible for regulating either pre-mRNA splicing or transcriptional activation. Interestingly, the CRTC1-MAML2 oncoprotein lacks the splicing domain and is incapable of altering splice-site selection despite robustly activating transcription. The differential usage of these distinct domains allows CRTCs to selectively mediate multiple facets of gene regulation, indicating that co-activators are not solely restricted to coordinating alternative splicing with increase in transcriptional activity.
| S-EPMC2750025 | biostudies-literature
Project description:BackgroundIndividual differences in human perception of sweetness are partly due to genetics; however, which genes are associated with the perception and the consumption of sweet substances remains unclear.ObjectiveThe aim of this study was to verify previous reported associations within genes involved in the peripheral receptor systems (i.e., TAS1R2, TAS1R3, and GNAT3) and reveal novel loci.MethodsWe performed genome-wide association scans (GWASs) of the perceived intensity of 2 sugars (glucose and fructose) and 2 high-potency sweeteners (neohesperidin dihydrochalcone and aspartame) in an Australian adolescent twin sample (n = 1757), and the perceived intensity and sweetness and the liking of sucrose in a US adult twin sample (n = 686). We further performed GWASs of the intake of total sugars (i.e., total grams of all dietary mono- and disaccharides per day) and sweets (i.e., handfuls of candies per day) in the UK Biobank sample (n = ≤174,424 white-British individuals). All participants from the 3 independent samples were of European ancestry.ResultsWe found a strong association between the intake of total sugars and the single nucleotide polymorphism rs11642841 within the FTO gene on chromosome 16 (P = 3.8 × 10-8) and many suggestive associations (P < 1.0 × 10-5) for each of the sweet perception and intake phenotypes. We showed genetic evidence for the involvement of the brain in both sweet taste perception and sugar intake. There was limited support for the associations with TAS1R2, TAS1R3, and GNAT3 in all 3 European samples.ConclusionsOur findings indicate that genes additional to those involved in the peripheral receptor system are also associated with the sweet taste perception and intake of sweet-tasting foods. The functional potency of the genetic variants within TAS1R2, TAS1R3, and GNAT3 may be different between ethnic groups and this warrants further investigations.
| S-EPMC6537940 | biostudies-literature