5/28/2023 0 Comments Pikka adren![]() Here we test their effectiveness in aged animals: 21-month-old female rats were treated with 500 mg GSPE/kg of body weight for ten days. Grape seed-derived procyanidins (GSPE) have been shown to be effective against several of these pathologies, mainly in young animal models. A chromatin immunoprecipitation (ChiP) assay showed that CTCF bound specifically to this region, a binding abrogated by zinc deficiency, suggesting that CTCF plays a critical role in zinc-dependent bitter taste perception through TAS2R8.Īdaptive homeostasis declines with age and this leads to, among other things, the appearance of chronic age-related pathologies such as cancer, neurodegeneration, osteoporosis, sarcopenia, cardiovascular disease and diabetes. Truncation/deletion mutants of TAS2R8 promoter-luciferase constructs showed that the region from nucleotide −1152 to nucleotide −925 was critical for intracellular zinc dependency and contained a CCCTC-binding factor (CTCF) binding motif. Treatment of the cells with N,N,N’,N’-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN), an intracellular chelator of Zn²⁺, in the presence of 10% fetal bovine serum reduced TAS2R8 promoter activity. Luciferase reporter assays showed that zinc deprivation inhibited TAS2R8 promoter activity, but not the promoter activity of the other two genes. The promoter activity of the TAS2R7, TAS2R8, and TAS2R42 genes were determined in Ca9-22 oral squamous cell carcinoma cells cultured in the presence or absence of zinc. The aim of this study was to investigate whether zinc deficiency affects the expression of TAS2R genes. Taste-2 receptors (TAS2Rs), which belong to the G-protein coupled receptor (GPCR) family, are receptors for bitter taste perception. We shall also discuss the therapeutic potential of novel TAS2Rs targets, which are appealing due to their ligand selectivity, expression pattern, or pharmacological profiles. Thus, the focus of this review is to provide an update on the expression and molecular basis of TAS2Rs functions in distinct extra-oral tissues in health and disease. The latest advances in taste receptor biology further raise the possibility of utilizing TAS2Rs as a therapeutic target or as an informative index to predict treatment responses in various disorders. The TAS2R cascade, for instance, has been recently considered to be a pivotal modulator of a number of (patho)physiological processes, including adipogenesis or carcinogenesis. Critical points of extra-oral TAS2Rs biology, such as their structure, roles, signaling transduction pathways, extensive mutational polymorphism, and molecular evolution, have been currently broadly studied. Although in the first instance, TAS2Rs were considered to be exclusively distributed in the apical microvilli of taste bud cells, numerous studies have detected these sensory receptor proteins in several extra-oral tissues, such as in pancreatic or ovarian tissues, as well as in their corresponding malignancies. These findings also have broader relevance for the study of taste GPCRs outside of the classical gustatory system, where understanding the mechanisms controlling the expression of these receptors may have implications for future therapeutic development.īitter taste-sensing type 2 receptors (TAS2Rs or T2Rs), belonging to the subgroup of family A G-protein coupled receptors (GPCRs), are of crucial importance in the perception of bitterness. Thus, combining cardiac gene expression data with bioinformatic analyses, this study has provided insights into the noncoding regulatory landscape for taste GPCRs. We also performed de novo motif enrichment in the proximal promoter regions and found several overrepresented DNA motifs in cardiac taste receptor gene promoters corresponding to ubiquitous and cardiac-specific transcription factor binding sites. We identified unique domains with strong regulatory potential in the vicinity of taste receptor genes. This chromosomal clustering mirrored the cardiac expression profile, suggesting that a common gene regulatory block may control the taste receptor locus. Gene expression analyses of healthy and diseased human and mouse hearts showed coordinated expression for a subset of chromosomally clustered taste receptors. ![]() Following our recent delineation of taste receptors in the heart, we investigated the genomic loci encoding for taste receptors to gain insight into the regulatory mechanisms that drive their expression in the heart. However, there is little known about the mechanisms governing the transcriptional regulation of taste receptor genes. Intriguingly, the taste receptors are also expressed outside of the oral cavity, including in the gut, airways, brain, and heart, where they have additional functions and contribute to disease. G protein-coupled receptors are the principal mediators of the sweet, umami, bitter, and fat taste qualities in mammals. ![]()
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