The Experts below are selected from a list of 249 Experts worldwide ranked by ideXlab platform
Yasuka Toda - One of the best experts on this subject based on the ideXlab platform.
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Positive/Negative Allosteric Modulation Switching in an Umami Taste Receptor (T1R1/T1R3) by a Natural Flavor Compound, Methional
Scientific Reports, 2018Co-Authors: Yasuka Toda, Tomoya Nakagita, Takatsugu Hirokawa, Yuki Yamashita, Ayako Nakajima, Masataka Narukawa, Yoshiro Ishimaru, Riichiro Uchida, Takumi MisakaAbstract:Taste is a vital sensation for vertebrates, enabling the detection of nutritionally important substances or potential toxins. A heteromeric complex of two class C GPCRs, T1R1 and T1R3, was identified as the umami (savory) taste receptor. Amino acids and 5′-ribonucleotides are well known to be natural ligands for human T1R1/T1R3. In this study, we reveal that Methional, which is a familiar flavor component in foods, is an allosteric modulator of T1R1/T1R3. Receptor expression experiments showed that Methional served as a positive allosteric modulator (PAM) of human T1R1/T1R3 and functioned as a negative allosteric modulator (NAM) of mouse T1R1/T1R3. Although amino acids and 5′-ribonucleotides bound to the extracellular domain of T1R1, the use of interspecies chimeric receptors demonstrated that Methional interacted with the transmembrane domain of T1R1. Site-directed mutagenesis and molecular modeling showed that Methional could potentially bind at two distinct sites in the transmembrane domain of T1R1 and that the amino acid residues in the bottom of the allosteric pocket engendered the switch between the PAM and NAM modes, which could contribute to switching the binding position of Methional. These results may be applicable for elucidating the molecular mechanisms underlying ligand recognition by other class C GPCRs.
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positive negative allosteric modulation switching in an umami taste receptor t1r1 t1r3 by a natural flavor compound Methional
Scientific Reports, 2018Co-Authors: Yasuka Toda, Tomoya Nakagita, Takatsugu Hirokawa, Yuki Yamashita, Ayako Nakajima, Masataka Narukawa, Yoshiro Ishimaru, Riichiro UchidaAbstract:Taste is a vital sensation for vertebrates, enabling the detection of nutritionally important substances or potential toxins. A heteromeric complex of two class C GPCRs, T1R1 and T1R3, was identified as the umami (savory) taste receptor. Amino acids and 5'-ribonucleotides are well known to be natural ligands for human T1R1/T1R3. In this study, we reveal that Methional, which is a familiar flavor component in foods, is an allosteric modulator of T1R1/T1R3. Receptor expression experiments showed that Methional served as a positive allosteric modulator (PAM) of human T1R1/T1R3 and functioned as a negative allosteric modulator (NAM) of mouse T1R1/T1R3. Although amino acids and 5'-ribonucleotides bound to the extracellular domain of T1R1, the use of interspecies chimeric receptors demonstrated that Methional interacted with the transmembrane domain of T1R1. Site-directed mutagenesis and molecular modeling showed that Methional could potentially bind at two distinct sites in the transmembrane domain of T1R1 and that the amino acid residues in the bottom of the allosteric pocket engendered the switch between the PAM and NAM modes, which could contribute to switching the binding position of Methional. These results may be applicable for elucidating the molecular mechanisms underlying ligand recognition by other class C GPCRs.
Riichiro Uchida - One of the best experts on this subject based on the ideXlab platform.
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Positive/Negative Allosteric Modulation Switching in an Umami Taste Receptor (T1R1/T1R3) by a Natural Flavor Compound, Methional
Scientific Reports, 2018Co-Authors: Yasuka Toda, Tomoya Nakagita, Takatsugu Hirokawa, Yuki Yamashita, Ayako Nakajima, Masataka Narukawa, Yoshiro Ishimaru, Riichiro Uchida, Takumi MisakaAbstract:Taste is a vital sensation for vertebrates, enabling the detection of nutritionally important substances or potential toxins. A heteromeric complex of two class C GPCRs, T1R1 and T1R3, was identified as the umami (savory) taste receptor. Amino acids and 5′-ribonucleotides are well known to be natural ligands for human T1R1/T1R3. In this study, we reveal that Methional, which is a familiar flavor component in foods, is an allosteric modulator of T1R1/T1R3. Receptor expression experiments showed that Methional served as a positive allosteric modulator (PAM) of human T1R1/T1R3 and functioned as a negative allosteric modulator (NAM) of mouse T1R1/T1R3. Although amino acids and 5′-ribonucleotides bound to the extracellular domain of T1R1, the use of interspecies chimeric receptors demonstrated that Methional interacted with the transmembrane domain of T1R1. Site-directed mutagenesis and molecular modeling showed that Methional could potentially bind at two distinct sites in the transmembrane domain of T1R1 and that the amino acid residues in the bottom of the allosteric pocket engendered the switch between the PAM and NAM modes, which could contribute to switching the binding position of Methional. These results may be applicable for elucidating the molecular mechanisms underlying ligand recognition by other class C GPCRs.
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positive negative allosteric modulation switching in an umami taste receptor t1r1 t1r3 by a natural flavor compound Methional
Scientific Reports, 2018Co-Authors: Yasuka Toda, Tomoya Nakagita, Takatsugu Hirokawa, Yuki Yamashita, Ayako Nakajima, Masataka Narukawa, Yoshiro Ishimaru, Riichiro UchidaAbstract:Taste is a vital sensation for vertebrates, enabling the detection of nutritionally important substances or potential toxins. A heteromeric complex of two class C GPCRs, T1R1 and T1R3, was identified as the umami (savory) taste receptor. Amino acids and 5'-ribonucleotides are well known to be natural ligands for human T1R1/T1R3. In this study, we reveal that Methional, which is a familiar flavor component in foods, is an allosteric modulator of T1R1/T1R3. Receptor expression experiments showed that Methional served as a positive allosteric modulator (PAM) of human T1R1/T1R3 and functioned as a negative allosteric modulator (NAM) of mouse T1R1/T1R3. Although amino acids and 5'-ribonucleotides bound to the extracellular domain of T1R1, the use of interspecies chimeric receptors demonstrated that Methional interacted with the transmembrane domain of T1R1. Site-directed mutagenesis and molecular modeling showed that Methional could potentially bind at two distinct sites in the transmembrane domain of T1R1 and that the amino acid residues in the bottom of the allosteric pocket engendered the switch between the PAM and NAM modes, which could contribute to switching the binding position of Methional. These results may be applicable for elucidating the molecular mechanisms underlying ligand recognition by other class C GPCRs.
Peter Schieberle - One of the best experts on this subject based on the ideXlab platform.
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Molecular Insights into Off-Flavor Formation during Pineapple Juice Processing
Flavour Science, 2014Co-Authors: Martin Steinhaus, Karin Thomas, Peter SchieberleAbstract:Application of a comparative aroma extract dilution analysis on a freshly prepared and a commercial pineapple juice suggested Methional as the compound mainly responsible for the cooked vegetable-like off-flavor frequently observed in industrially processed pineapple juices. Lab-scale pasteurization experiments showed that Methional is thermally formed from methionine during processing.
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Quantitation of odor-active compounds in rye flour and rye sourdough using stable isotope dilution assays.
Journal of agricultural and food chemistry, 2002Co-Authors: Eva Kirchhoff, Peter SchieberleAbstract:Application of the aroma extract dilution analysis on a flavor distillate prepared from freshly ground rye flour (type 1150) revealed 1-octen-3-one (mushroom-like), Methional (cooked potato), and (E)-2-nonenal (fatty, green) with the highest flavor dilution (FD) factors among the 26 odor-active volatiles identified. Quantitative measurements performed by stable isotope dilution assays and a comparison to the odor thresholds of selected odorants in starch suggested Methional, (E)-2-nonenal, and hexanal as contributors to the flour aroma, because their concentrations exceeded their odor thresholds by factors >100. Application of the same approach on a rye sourdough prepared from the same batch of flour revealed 3-methylbutanal, vanillin, 3-methylbutanoic acid, Methional, (E,E)-2,4-decadienal, 2,3-butanedione, and acetic acid as important odorants; their concentrations exceeded their odor thresholds in water and starch by factors >100. A comparison of the concentrations of 20 odorants in rye flour and the sourdough made therefrom indicated that flour, besides the fermentation process, is an important source of aroma compounds in dough. However, 3-methylbutanol, acetic acid, and 2,3-butanedione were much increased during fermentation, whereas (E,E)-2,4-decadienal and 2-methylbutanal were decreased. Similar results were obtained for five different flours and sourdoughs, respectively, although the amounts of some odorants in the flour and the sourdough differed significantly within batches.
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studies on the key odorants formed by roasting of wild mango seeds irvingia gabonensis
Journal of Agricultural and Food Chemistry, 2000Co-Authors: A O Tairu, T. Hofmann, Peter SchieberleAbstract:Application of the aroma extract dilution analysis on a concentrate of volatiles obtained by solvent extraction and high vacuum distillation from roasted seeds (180 °C; 15 min) of wild mango (Irvingia gabonensis) revealed 32 odor-active compounds with flavor dilution (FD) factors ranging from 8 (low odor activity) to 2048 (high odor activity). The identification experiments based on the use of reference odorants revealed Methional (cooked potato-like) followed by 2-acetyl-1-pyrroline (roasty, popcorn-like), butan-2,3-dione, pentan-2,3-dione, 2-ethyl-3,5-dimethylpyrazine, and 2,3-diethyl-5-methylpyrazine as the key aroma compounds among the 27 odorants identified. All odorants are reported for the first time as components of roasted wild mango seeds. Keywords: Wild mango; Irvingia gabonensis; aroma extract dilution analysis; Methional; 2-acetyl-1-pyrroline
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Potent odorants of rye bread crust-differences from the crumb and from wheat bread crust
Zeitschrift für Lebensmittel-Untersuchung und Forschung, 1994Co-Authors: Peter Schieberle, Werner GroschAbstract:Aroma extract dilution analyses revealed twenty-eight odorants in fresh rye bread crust and twenty in its crumb. On the basis of high flavour dilution factors, Methional (boiled potato), 3-methylbutanal (malty), (E)-2-nonenal (green, tallowy), (E,E)-2,4-decadienal (fatty) and acetic acid (sour, pungent) belonged to the potent odorants of the crust, and phenylacetaldehyde, (E)-2-nonenal and (E,E)-2,4-decadienal to those of the crumb. Compared with the crust, especially the odour activities of Methional, 3-methylbutanal, 2-ethyl-3,5-dimethyl-pyrazine and 4-hydroxy-2,5-dimethyl-3(2H)-furanone were significantly lower in the crumb. Calculation of the odour activity values (OAV; ratio of concentration to odour threshold) indicated that the higher OAV of Methional in the rye crust and the higher OAV of 2-acetyl-1-pyrroline in the wheat bread crust mainly contributed to the flavour difference of the two kinds of bread. Aromaextraktverdünnungsanalysen ergaben 28 Geruchsstoffe in frischer Roggenbrotkruste und 20 in der Krume. Aufgrund hoher FD-Faktoren gehörten Methional (gekochte Kartoffel), 3-Methylbutanal (malzartig), (E)-2-Nonenal (grün, talgig), (E,E)-2,4-De-cadienal (fettig) und Essigsäure (sauer, stechend) zu den potenten Geruchsstoffen der Kruste sowie Phenylacetal-dehyd, (E)-2-Nonenal und (E,E)-2,4-Decadienal zu denen der Krume. Im Vergleich zur Kruste waren insbesondere die Geruchsaktivitäten von Methional, 3-Methylbutanal, 2-Ethyl-3,5-dimethylpyrazin und 4-Hydroxy-2,5-dimethyl-3 (2H)-furanon in der Krume deutlich erniedrigt.-Die Berechnung von Aromawerten (Quotient aus Konzentration und Geruchsschwelle) zeigte, daß insbesondere der erheblich höhere Aromawert des Methionals in der Roggenbrotkruste und der des röstig, süß riechenden 2-Acetyl-1-pyrrolins in der Weißbrotkruste wesentlich zum Aromaunterschied beider Brotarten beiträgt.
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Potent odorants of rye bread crust-differences from the crumb and from wheat bread crust
Zeitschrift f�r Lebensmittel-Untersuchung und -Forschung, 1994Co-Authors: Peter Schieberle, Werner GroschAbstract:Aroma extract dilution analyses revealed twenty-eight odorants in fresh rye bread crust and twenty in its crumb. On the basis of high flavour dilution factors, Methional (boiled potato), 3-methylbutanal (malty), (E)-2-nonenal (green, tallowy), (E,E)-2,4-decadienal (fatty) and acetic acid (sour, pungent) belonged to the potent odorants of the crust, and phenylacetaldehyde, (E)-2-nonenal and (E,E)-2,4-decadienal to those of the crumb. Compared with the crust, especially the odour activities of Methional, 3-methylbutanal, 2-ethyl-3,5-dimethyl-pyrazine and 4-hydroxy-2,5-dimethyl-3(2H)-furanone were significantly lower in the crumb. Calculation of the odour activity values (OAV; ratio of concentration to odour threshold) indicated that the higher OAV of Methional in the rye crust and the higher OAV of 2-acetyl-1-pyrroline in the wheat bread crust mainly contributed to the flavour difference of the two kinds of bread.
Tomoya Nakagita - One of the best experts on this subject based on the ideXlab platform.
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Positive/Negative Allosteric Modulation Switching in an Umami Taste Receptor (T1R1/T1R3) by a Natural Flavor Compound, Methional
Scientific Reports, 2018Co-Authors: Yasuka Toda, Tomoya Nakagita, Takatsugu Hirokawa, Yuki Yamashita, Ayako Nakajima, Masataka Narukawa, Yoshiro Ishimaru, Riichiro Uchida, Takumi MisakaAbstract:Taste is a vital sensation for vertebrates, enabling the detection of nutritionally important substances or potential toxins. A heteromeric complex of two class C GPCRs, T1R1 and T1R3, was identified as the umami (savory) taste receptor. Amino acids and 5′-ribonucleotides are well known to be natural ligands for human T1R1/T1R3. In this study, we reveal that Methional, which is a familiar flavor component in foods, is an allosteric modulator of T1R1/T1R3. Receptor expression experiments showed that Methional served as a positive allosteric modulator (PAM) of human T1R1/T1R3 and functioned as a negative allosteric modulator (NAM) of mouse T1R1/T1R3. Although amino acids and 5′-ribonucleotides bound to the extracellular domain of T1R1, the use of interspecies chimeric receptors demonstrated that Methional interacted with the transmembrane domain of T1R1. Site-directed mutagenesis and molecular modeling showed that Methional could potentially bind at two distinct sites in the transmembrane domain of T1R1 and that the amino acid residues in the bottom of the allosteric pocket engendered the switch between the PAM and NAM modes, which could contribute to switching the binding position of Methional. These results may be applicable for elucidating the molecular mechanisms underlying ligand recognition by other class C GPCRs.
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positive negative allosteric modulation switching in an umami taste receptor t1r1 t1r3 by a natural flavor compound Methional
Scientific Reports, 2018Co-Authors: Yasuka Toda, Tomoya Nakagita, Takatsugu Hirokawa, Yuki Yamashita, Ayako Nakajima, Masataka Narukawa, Yoshiro Ishimaru, Riichiro UchidaAbstract:Taste is a vital sensation for vertebrates, enabling the detection of nutritionally important substances or potential toxins. A heteromeric complex of two class C GPCRs, T1R1 and T1R3, was identified as the umami (savory) taste receptor. Amino acids and 5'-ribonucleotides are well known to be natural ligands for human T1R1/T1R3. In this study, we reveal that Methional, which is a familiar flavor component in foods, is an allosteric modulator of T1R1/T1R3. Receptor expression experiments showed that Methional served as a positive allosteric modulator (PAM) of human T1R1/T1R3 and functioned as a negative allosteric modulator (NAM) of mouse T1R1/T1R3. Although amino acids and 5'-ribonucleotides bound to the extracellular domain of T1R1, the use of interspecies chimeric receptors demonstrated that Methional interacted with the transmembrane domain of T1R1. Site-directed mutagenesis and molecular modeling showed that Methional could potentially bind at two distinct sites in the transmembrane domain of T1R1 and that the amino acid residues in the bottom of the allosteric pocket engendered the switch between the PAM and NAM modes, which could contribute to switching the binding position of Methional. These results may be applicable for elucidating the molecular mechanisms underlying ligand recognition by other class C GPCRs.
Gerard Quash - One of the best experts on this subject based on the ideXlab platform.
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Methionine-derived metabolites in apoptosis: therapeutic opportunities for inhibitors of their metabolism in chemoresistant cancer cells.
Current medicinal chemistry, 2009Co-Authors: Gerard Quash, Guy FournetAbstract:Methionine, in addition to its role in protein synthesis, participates in 3 important cellular functions: as AdoMet in transmethylation; as decarboxylated-AdoMet in aminopropylation; as homocysteine its demethylated form, in trans-sulphuration. Here we provide evidence from the literature and from our own work for a fourth role for its oxoacid: 4-methylthio-2-oxo-butanoate (MTOB) in apoptosis [28,29]. MTOB enters 2 pathways: (a) transamination by glutamine-transaminase K to methionine[13,14].(b)oxidative decarboxylation by the mitochondrial Branched-Chain-Oxo-Acid-Dehydrogenase-Complex to Methional and finally to methylthiopropanoyl CoA (MTPCoA) [26,27]. Some of the Methional formed after MTOB decarboxylation leaks into the cytoplasm as free Methional [29]. Exogenous Methional induces apoptosis in normal and cancer cells in culture [28, 29] but not in those overexpressing the antiapoptotic gene bcl2 [30]. In physiologically-induced apoptosis e.g; trophic factor (IL3) withdrawal, Methional leakage is decreased [29] suggesting that MTPCoA is also involved in apoptosis. Both Methional and MTPCoA give rise to metabolites that may act as cross-linking agents. In the case of Methional, the CH3-S moiety is lost and malondialdehyde (MDA) is formed when Methional is subjected to ( )OH attack [29]. MDA generated in situ from 1,3-propanediol, induces DNA-protein cross-linking [41].With regard to MTPCoA, it is metabolized to malonic semialdehyde CoA (MASACoA) with loss of the CH3-S moiety [48,49]. The capacity of MASACoA to form cross-links has not yet been established experimentally, but it could be a substrate for one of the histone acyl transferases [50, 51] and so form amides via the CoA at one end and imines by its CHO group at the other, with amino groups on proteins. Chromatin cross-linking/condensation is one of the hall-marks of apoptosis [40]. Methional, MDA and other apoptogenic aldehydes like 4-hydroxy-2-nonenal are oxidized by ALDHs to non-apoptogenic carboxylic acids [29,44, 45,68] but retain their apoptotic activity when the ALDHs are inhibited [98,110]. MASACoA would also lose its cross-linking capacity if its CoA moiety were putatively hydrolysed by ALDHs and/or acylCoA thioesterases [56,58,88,89]. ALDH inhibitors that control cellular MDA and possibly MASACoA homeostasis are cited as examples of targeted therapeutic approaches in chemoresistant cancers [62,84,97,98,110].
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A thioester analogue of an amino acetylenic aldehyde is a suicide inhibitor of aldehyde dehydrogenase and an inducer of apoptosis in mouse lymphoid cells overexpressing the bcl2 gene.
Advances in experimental medicine and biology, 1999Co-Authors: Gerard Quash, Guy Fournet, Catherine Raffin, Jacqueline Chantepie, Yvonne Michal, I Jacques Gore, Uwe ReichertAbstract:We have previously shown that Methional, CH3SCH2CH2CHO, an endogeneous cellular aldehyderived by the oxidative decarboxylation of 4-methylthio-2-oxobutanoic acid (B), an intermediate in the methionine salvage pathway is a potent inducer of apoptosis when added to cultures of mouse lymphoid cells BAF3 bo (Quash et al., 1995). MTOB a00 μM was also capable of alleviating the methionine dependence shown by transfed cells (Ogier et al., 1993) because of its ready transamination to methionine, with gamine as amine donor (Backlund et al., 1982). Further, the inhibition of this MTOB transaminase with novel transition state inhibitors such as methionine-ethyl ester- pyridoxal induced apoptosis in BAF3 bo cells but not in BAF3 bcl2 which had been trans- fected with the human bcl2 gene (Roch et al., 1996). When the reasons for this refractory behaviour of BAF3 bcl2 were investigated using[14C] MTOB it was found that the production of [14Methional from [14C] MTOB was reduced by 50% in BAF3 bcl2 and that even the direct addition of 600μM Methional could not induce apoptosis in BAF3 bcl2 (Roch and al, 19 Methional is itself further metabolised intracellularly [Figure 1] by 3 pathways: reduction by aldehyde reductase (ALR) to methionol, oxidation by aldehyde dehydro- genaseLDH1) to methyl thiopropionic acid and β-hydroxylation to malondialdehyde. We therefore tried to see whether the inhibition of the reductase or the dehydrogenase would uce apoptosis in Methional treated BAF3 bcl2 cells. Using quercitin as an inhibitor of ALR increase in apotosis was observed in BAF3 bcl2, but this result is to be interpreted with caution as quercitin also induces DNA strand breaks directly.With disulfiram as an ibitor of ALDH a small increase was seen but experimentation could be carried out only with low concentrations (< 100μM) due to the intrinsic toxicity of this compound. It was therefore clear that more specific inhibitors of ALDH were required to try to determine if ALDH played a role in the resistance to the apoptosis-inducing activity of methio.
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Methional, a cellular metabolite, induces apoptosis preferentially in G2/M‐Synchronized BAF3 murine lymphoid cells
Cytometry, 1998Co-Authors: A M Roch, Yvonne Michal, Geneviève Panaye, Gerard QuashAbstract:We have previously shown that Methional, derived from 4-methylthio-2-oxobutanoate, is a cellular mediator of apoptosis in BAF3 b0 murine lymphoid cells, which are dependent on IL3 for their growth in culture. When cells synchronized in S phase by double thymidine block were treated with Methional immediately after thymidine withdrawal, Methional was unable to induce DNA-strand breaks, whereas it inhibited the progression of cells from S to G2/M phases. This inhibition of cell cycle progression was associated with a 53% decrease in DNA synthesis. In contrast, when BAF3 b0 cells were synchronized in G2/M phase using SK&F 96365, and treated with Methional immediately after drug removal, Methional induced DNA-strand breaks in 49% of cells in 4 h, compared to 12% in controls. As contact time increased from 4 to 8 h, DNA-strand breaks increased to 94% in Methional-treated cells compared to 11% in controls. These observations on G2/M-synchronized cells are different from those seen in BAF3b0 cells in G1 phase, 3 h after their release from the G2/M block, in that there was no decrease in size of the G1 population even after an additional 4 h incubation in the presence of Methional. These results, taken together, provide a rational basis for using combinations of Methional and G2/M blockers as inducers of DNA-strand breaks and apoptosis in murine lymphoid cells. Cytometry 31:10–19, 1998. © 1998 Wiley-Liss, Inc.
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Methional a cellular metabolite induces apoptosis preferentially in g2 m synchronized baf3 murine lymphoid cells
Cytometry, 1998Co-Authors: A M Roch, Yvonne Michal, Geneviève Panaye, Gerard QuashAbstract:We have previously shown that Methional, derived from 4-methylthio-2-oxobutanoate, is a cellular mediator of apoptosis in BAF3 b0 murine lymphoid cells, which are dependent on IL3 for their growth in culture. When cells synchronized in S phase by double thymidine block were treated with Methional immediately after thymidine withdrawal, Methional was unable to induce DNA-strand breaks, whereas it inhibited the progression of cells from S to G2/M phases. This inhibition of cell cycle progression was associated with a 53% decrease in DNA synthesis. In contrast, when BAF3 b0 cells were synchronized in G2/M phase using SK&F 96365, and treated with Methional immediately after drug removal, Methional induced DNA-strand breaks in 49% of cells in 4 h, compared to 12% in controls. As contact time increased from 4 to 8 h, DNA-strand breaks increased to 94% in Methional-treated cells compared to 11% in controls. These observations on G2/M-synchronized cells are different from those seen in BAF3b0 cells in G1 phase, 3 h after their release from the G2/M block, in that there was no decrease in size of the G1 population even after an additional 4 h incubation in the presence of Methional. These results, taken together, provide a rational basis for using combinations of Methional and G2/M blockers as inducers of DNA-strand breaks and apoptosis in murine lymphoid cells. Cytometry 31:10–19, 1998. © 1998 Wiley-Liss, Inc.
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Methional derived from 4-methylthio-2-oxobutanoate is a cellular mediator of apoptosis in BAF3 lymphoid cells.
Biochemical Journal, 1995Co-Authors: Gerard Quash, Guy Fournet, Jacqueline Chantepie, Yvonne Michal, A M Roch, C DumontetAbstract:4-Methylthio-2-oxobutanoic acid is the direct precursor of Methional, which is a potent inducer of apoptosis in a BAF3 murine lymphoid cell line which is interleukin-3 (IL3)-dependent. Cultures treated for 8 h with Methional in the presence of IL3 show extensive DNA double-strand breaks on flow cytometric analysis, increases in DNA fragmentation as measured by the amount of non-sedimentable DNA present in the 30,000 g supernatant of cell lysates and the typical laddering pattern of multiples of 180 bp seen upon agarose gel electrophoresis. No such features of apoptosis were found in cells treated with 4-methylthio 2-oxobutanoic acid or propanal, suggesting that the simultaneous presence of the methylthio group on the propanal moiety is essential for apoptosis to take place. Methional is further metabolized in cells by two reactions: oxidation via aldehyde dehydrogenase to (methylthio)propionic acid or beta-hydroxylation to malondialdehyde. The formation of malondialdehyde from Methional in vitro by chemical hydroxylation under the conditions of the Fenton reaction provides a mechanism for the beta-hydroxylation which takes place in vivo. During apoptosis induced by IL3 deprivation, the ratio of 2,4-DNPH MDA to 2,4-DNPH Methional is 0.94 in cells in IL3- medium compared with 0.54 in cells in IL3+ medium. These results support a role of cellular Methional and malondialdehyde in apoptosis.