Responsiveness to 6-n-Propylthiouracil (PROP) Is Associated with Salivary Levels of Two Specific Basic Proline-Rich Proteins in Humans

PLOS ONE, Dec 2019

Thiourea tasting can be predictive of individual differences in bitter taste responses, general food preferences and eating behavior, and could be correlated with saliva chemical composition. We investigated the possible relationship between PROP bitter taste responsiveness and the salivary proteome in subjects genotyped for TAS2R38 and gustin gene polymorphisms. Taste perception intensity evoked by PROP and NaCl solutions was measured in sixty-three volunteers (21 males, 42 females, age 25±3 y) to establish their PROP taster status, and 24 PROP super-tasters and 21 nontasters were selected to participate in the study. TAS2R38 and gustin gene molecular analysis were performed using PCR techniques. Qualitative and quantitative determination of salivary proteins was performed by HPLC-ESI-MS before and after PROP taste stimulation. PROP super-tastings was strongly associated with the ‘taster’ variant (PAV haplotype) of TAS2R38 and the A allele of rs2274333 polymorphism in the gustin gene and nontasting was associated with the minor alleles at both loci. ANOVA revealed that basal levels of II-2 and Ps-1 proteins, belonging to the basic proline-rich protein (bPRPs) family, were significantly higher in PROP super-taster than in nontaster un-stimulated saliva, and that PROP stimulation elicited a rapid increase in the levels of these same proteins only in PROP super-taster saliva. These data show for the first time that responsiveness to PROP is associated with salivary levels of II-2 peptide and Ps-1 protein, which are products of the PRB1 gene. These findings suggest that PRB1, in addition to TAS2R38 and gustin, could contribute to individual differences in thiourea sensitivity, and the expression of the PROP phenotype as a complex genetic trait.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0030962&type=printable

Responsiveness to 6-n-Propylthiouracil (PROP) Is Associated with Salivary Levels of Two Specific Basic Proline-Rich Proteins in Humans

et al. (2012) Responsiveness to 6-n-Propylthiouracil (PROP) Is Associated with Salivary Levels of Two Specific Basic Proline-Rich Proteins in Humans. PLoS ONE 7(2): e30962. doi:10.1371/journal.pone.0030962 Responsiveness to 6-n-Propylthiouracil (PROP) Is Associated with Salivary Levels of Two Specific Basic Proline-Rich Proteins in Humans Tiziana Cabras 0 Melania Melis 0 Massimo Castagnola 0 Alessandra Padiglia 0 Beverly J. Tepper 0 Irene Messana 0 Iole Tomassini Barbarossa 0 Wolfgang Meyerhof, German Institute for Human Nutrition, Germany 0 1 Department of Life and Environment Sciences, Macrosection of Biomedicine, University of Cagliari , Monserrato, Cagliari , Italy , 2 Department of Biomedical Sciences, University of Cagliari , Monserrato, Cagliari , Italy , 3 Institute of Biochemistry and Clinical Biochemistry, Catholic University , Rome , Italy , 4 Department of Food Science, School of Environmental and Biological Sciences, Rutgers University , New Brunswick, New Jersey , United States of America Thiourea tasting can be predictive of individual differences in bitter taste responses, general food preferences and eating behavior, and could be correlated with saliva chemical composition. We investigated the possible relationship between PROP bitter taste responsiveness and the salivary proteome in subjects genotyped for TAS2R38 and gustin gene polymorphisms. Taste perception intensity evoked by PROP and NaCl solutions was measured in sixty-three volunteers (21 males, 42 females, age 2563 y) to establish their PROP taster status, and 24 PROP super-tasters and 21 nontasters were selected to participate in the study. TAS2R38 and gustin gene molecular analysis were performed using PCR techniques. Qualitative and quantitative determination of salivary proteins was performed by HPLC-ESI-MS before and after PROP taste stimulation. PROP super-tastings was strongly associated with the 'taster' variant (PAV haplotype) of TAS2R38 and the A allele of rs2274333 polymorphism in the gustin gene and nontasting was associated with the minor alleles at both loci. ANOVA revealed that basal levels of II-2 and Ps-1 proteins, belonging to the basic proline-rich protein (bPRPs) family, were significantly higher in PROP super-taster than in nontaster un-stimulated saliva, and that PROP stimulation elicited a rapid increase in the levels of these same proteins only in PROP super-taster saliva. These data show for the first time that responsiveness to PROP is associated with salivary levels of II-2 peptide and Ps-1 protein, which are products of the PRB1 gene. These findings suggest that PRB1, in addition to TAS2R38 and gustin, could contribute to individual differences in thiourea sensitivity, and the expression of the PROP phenotype as a complex genetic trait. - Funding: This work was supported by the Italian Ministry of University and Research, Fondazione Banco di Sardegna and Nando Peretti Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Plants produce a large diversity of bitter-tasting compounds as protection against predation [1]. These substances include bitter alkaloids such as quinine and brucine, isothiocyanates from cabbage and mustard seeds, as well as certain fatty acids, amino acids and peptides, to name a few [24]. Since many bitter-tasting substances can be toxic, the ability of humans to detect bitterness at low concentrations represents an important evolutionary adaptation for limiting or avoiding the consumption plant foods that could be harmful [5]. On the other hand, several classes of bitter polyphenols found in tea, coffee, dark-colored fruit, citrus and chocolate [6] provide positive health benefits by acting as antibacterials and antioxidants [7]. Bitter taste is mediated by the TAS2R sub-family of G proteincoupled receptors [8,9]. Humans posses ,25 TAS2R bitter receptors encoded by clusters of genes located on chromosomes 5p, 7q, 12p [10]. So far, more than 550 ligands for human bitter receptors have been identified [11]. However, this number represents only a tiny fraction of the thousands of plant-based bitter compounds that exist in nature. Since the number of compounds greatly exceeds the number of receptors, it seems likely that individual receptors respond to more than one bitter compound type [12]. In fact, some receptors are narrowly-tuned, responding to a limited range of compounds. TAS2R8 is an example of a highly-selective receptor that has only 3 known ligands which share common structural properties. On the opposite end of the spectrum are TAS2R10, -14 and -46 which are highly promiscuous, responding to 50% of the bitter compounds applied in cell-based expression studies. TAS2R38, the receptor that binds the N-C = S moiety of the bitter thiourea compounds phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) [13 (...truncated)


This is a preview of a remote PDF: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0030962&type=printable

Tiziana Cabras, Melania Melis, Massimo Castagnola, Alessandra Padiglia, Beverly J. Tepper, Irene Messana, Iole Tomassini Barbarossa. Responsiveness to 6-n-Propylthiouracil (PROP) Is Associated with Salivary Levels of Two Specific Basic Proline-Rich Proteins in Humans, PLOS ONE, 2012, 2, DOI: 10.1371/journal.pone.0030962