Evolution of the primate glutamate taste sensor from a nucleotide sensor

霊長類におけるグルタミン酸の旨味の起源 --体の大きな霊長類は旨味感覚で葉の苦さを克服--. 京都大学プレスリリース. 2021-08-30.Taste perception plays an essential role in food selection. Umami (savory) tastes are sensed by a taste receptor complex, T1R1/T1R3, that detects proteinogenic amino acids. High sensitivity to l-glutamate (l-Glu) is a characteristic of human T1R1/T1R3, but the T1R1/T1R3 of other vertebrates does not consistently show this l-Glu response. Here, we demonstrate that the l-Glu sensitivity of T1R1/T1R3 is a derived state that has evolved repeatedly in large primates that rely on leaves as protein sources, after their divergence from insectivorous ancestors. Receptor expression experiments show that common amino acid substitutions at ligand binding sites that render T1R1/T1R3 sensitive to l-Glu occur independently at least three times in primate evolution. Meanwhile T1R1/T1R3 senses 5′-ribonucleotides as opposed to l-Glu in several mammalian species, including insectivorous primates. Our chemical analysis reveal that l-Glu is one of the major free amino acids in primate diets and that insects, but not leaves, contain large amounts of free 5′-ribonucleotides. Altering the ligand-binding preference of T1R1/T1R3 from 5′-ribonucleotides to l-Glu might promote leaf consumption, overcoming bitter and aversive tastes. Altogether, our results provide insight into the foraging ecology of a diverse mammalian radiation and help reveal how evolution of sensory genes facilitates invasion of new ecological niches

Information provision and kidney donor and recipient decision making

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5

Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2)–deficient (Nrf2−⧸−) mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2−⧸− mouse livers were lower than that in wild-type mouse livers. Nrf2−⧸− mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression

Effects of GDS-23 on Nrf2 gene expressions.

NHEKs were treated with 50 μM GDS-23 for 12 and 24 h. Control cells were treated with vehicle. Nrf2 mRNA levels were analyzed using qPCR. Results are expressed as mean ± S.D. (n = 4). Significance; *p t-test). GDS-23, glyceryl polyethylene glycol-23 distearate; NHEK, normal human epidermal keratinocyte; Nrf2, nuclear factor E2-related factor-2. (TIF)</p

Primers used in quantitative polymerase chain reaction.

Primers used in quantitative polymerase chain reaction.</p

Effects of GDS-23 on the expression of genes involved in antioxidative stress responses.

NHEKs were treated with either 25 or 50 μM GDS-23 for 12, 18, 24, 30, 36, and 48 h. Control cells were treated with vehicle. mRNA levels of HO-1, NQO1, GCLC, CAT, and PPARγ were analyzed using quantitative polymerase chain reaction. Results are expressed as mean ± standard deviation (n = 4). Significance; *p < 0.05, **p < 0.01, ***p < 0.001 vs. control cells (Dunnett’s test). GDS-23, glyceryl polyethylene glycol-23 distearate; NHEK, normal human epidermal keratinocyte; HO-1, heme oxygenase-1; NQO1, NAD(P)H-quinone oxidoreductase 1; GCLC, glutamate-cysteine ligase catalytic subunit; CAT, catalase; PPARγ, peroxisome proliferator-activated receptor γ.</p

Evaluation of GDS-23 cytotoxicity and protein quantification in keratinocytes.

NHEKs were treated with GDS-23 at concentrations ranging from 12.5 to 200 μM for 24 h, and cytotoxicity was evaluated using a neutral red assay. Results are expressed as a percentage survival compared to the control cells and as mean ± S.D. (n = 6). Significance; **p (TIF)</p

Typical structural formula of diacylglycerol polyethylene glycol adduct.

Typical structural formula of diacylglycerol polyethylene glycol adduct.</p