Bitter taste receptors: Extraoral roles in pathophysiology

Shaik, Feroz Ahmed; Singh, Nisha; Arakawa, Makoto; Duan, Kangmin; Bhullar, Rajinder P.; Chelikani, Prashen

doi:10.1016/j.biocel.2016.03.011

Cited by 85 publications

(66 citation statements)

References 94 publications

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“…When a bitter agonist of TAS2Rs was applied to individuals with asthma, suppressed abnormal contraction of airway smooth muscle, and inhibited release of inflammatory cytokines via mast cell inactivation were observed [5, 42]. Recently, several studies have also described the expression and roles of TAS2Rs in several cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it will be important for future studies to investigate the function of these receptors in various tissues and to further characterize the discrepancy observed in the present study. Structure-function studies have provided valuable insight into the potential functions of the 25 known TAS2Rs [42, 68]. However, fewer biochemical, pathophysiological, and pharmacological studies have been conducted.…”

Section: Discussionmentioning

confidence: 99%

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Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells

et al. 2017

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Neuroblastoma (NB) originates from immature neuronal cells and currently has a poor clinical outcome. NB cells possess cancer stem cells (CSCs) characteristics that facilitate the initiation of a tumor, as well as its metastasis. Human bitter taste receptors, referred to as TAS2Rs, are one of five types of basic taste receptors and they belong to a family of G-protein coupled receptors. The recent finding that taste receptors are expressed in non-gustatory tissues suggest that they mediate additional functions distinct from taste perception. While it is generally admitted that the recognition of bitter tastes may be associated with a self-defense system to prevent the ingestion of poisonous food compounds, this recognition may also serve as a disease-related function in the human body. In particular, the anti-cancer stemness and invasion effects of TAS2Rs on NB cells remain poorly understood. In the present study, endogenous expression of TAS2R8 and TAS2R10 in SK-N-BE(2)C and SH-SY5Y cells was examined. In addition, higher levels of TAS2R8 and TAS2R10 expression were investigated in more differentiated SY5Y cells. Both TAS2Rs were up-regulated following the induction of neuronal cell differentiation by retinoic acid. In addition, ectopic transfection of the two TAS2Rs induced neurite elongation in the BE(2)C cells, and down-regulated CSCs markers (including DLK1, CD133, Notch1, and Sox2), and suppressed self-renewal characteristics. In particular, TAS2RS inhibited tumorigenicity. Furthermore, when TAS2Rs was over-expressed, cell migration, cell invasion, and matrix metalloproteinases activity were inhibited. Expression levels of hypoxia-inducible factor-1α, a well-known regulator of tumor metastasis, as well as its downstream targets, vascular endothelial growth factor and glucose transporter-1, were also suppressed by TAS2Rs. Taken together, these novel findings suggest that TAS2Rs targets CSCs by suppressing cancer stemness characteristics and NB cell invasion, thereby highlighting the chemotherapeutic potential of bitter taste receptors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells

et al. 2017

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“…In humans, bitter taste is perceived by 25 distinct T2Rs. They are expressed in the oral cavity, gastrointestinal neuroendocrine cells of the large intestine and in many extraoral tissues [8,9]. T2Rs typically consist of 290-333 amino acids and display considerable degree of evolutionary divergence [10].…”

Section: Introductionmentioning

confidence: 99%

Cholesterol modulates bitter taste receptor function

Pydi¹,

Jafurulla²,

Wai³

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Bitter taste perception in humans is believed to act as a defense mechanism against ingestion of potential toxic substances. Bitter taste is perceived by 25 distinct bitter taste receptors (T2Rs) which belong to the family of G protein-coupled receptors (GPCRs). In the overall context of the role of membrane lipids in GPCR function, we show here that T2R4, a representative member of the bitter taste receptor family, displays cholesterol sensitivity in its signaling function. In order to gain further insight into cholesterol sensitivity of T2R4, we mutated two residues Tyr114(3.59) and Lys117(3.62) present in the cholesterol recognition amino acid consensus (CRAC) motif in T2R4 with alanines. We carried out functional characterization of the mutants by calcium mobilization, followed by cholesterol depletion and replenishment. CRAC motifs in GPCRs have previously been implicated in preferential cholesterol association. Our analysis shows that the CRAC motif represents an intrinsic feature of bitter taste receptors and is conserved in 22 out of 25 human T2Rs. We further demonstrate that Lys117, an important CRAC residue, is crucial in the reported cholesterol sensitivity of T2R4. Interestingly, cholesterol sensitivity of T2R4 was observed at quinine concentrations in the lower mM range. To the best of our knowledge, our results represent the first report addressing the molecular basis of cholesterol sensitivity in the function of taste receptors.

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“…in respiratory tract infections, rhinosinuitis, alcohol dependence, various forms of cancers, cystic fibrosis (studies of TAS2R expressions in this context show promising future drug-target perspectives) (Shaik et al, 2016).…”

Section: Bitter Taste Receptors -Signalling the Presence Of Xenobiotimentioning

confidence: 99%

Taste receptors in the gut – A new target for health promoting properties in diet

Ekstrand

Young

Rasmussen

2017

Food Research International

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These receptors are involved in an intricate signalling network for monitoring of taste and nutrient intake, homeostasis and energy metabolism, and they are also an early warning system for toxic substances in our diet. Especially the receptors for bitter taste provide a new possibility to activate a number of health related signalling pathways, already at low concentrations of the active substance, without requiring uptake into the body and transport via the circulation. When ligands bind to these receptors, signalling is induced either via peptide hormones into the circulation to other organs in the body, or via nerve fibers directly to the brain.

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Bitter taste receptors: Extraoral roles in pathophysiology

Cited by 85 publications

References 94 publications

Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells

Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells

Cholesterol modulates bitter taste receptor function

Taste receptors in the gut – A new target for health promoting properties in diet

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