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Acta Pharmacologica Sinica Aug 2021Propionate is a short-chain fatty acid (SCFA) mainly produced from carbohydrates by gut microbiota. Sodium propionate (SP) has shown to suppress the invasion in G...
Propionate is a short-chain fatty acid (SCFA) mainly produced from carbohydrates by gut microbiota. Sodium propionate (SP) has shown to suppress the invasion in G protein-coupled receptor 41 (GPR41) and GPR43-overexpressing breast cancer cells. In this study we investigated the effects of SP on the proliferation, apoptosis, autophagy, and antioxidant production of breast cancer cells. We showed that SP (5-20 mM) dose-dependently inhibited proliferation and induced apoptosis in breast cancer cell lines JIMT-1 (ER-negative and HER2-expressing) and MCF7 (ER-positive type), and this effect was not affected by PTX, thus not mediated by the GPR41 or GPR43 SCFA receptors. Meanwhile, we demonstrated that SP treatment increased autophagic and antioxidant activity in JIMT-1 and MCF7 breast cancer cells, which might be a compensatory mechanism to overcome SP-induced apoptosis, but were not sufficient to overcome SP-mediated suppression of proliferation and induction of apoptosis. We revealed that the anticancer effect of SP was mediated by inhibiting JAK2/STAT3 signaling which led to cell-cycle arrest at G/G phase, and increasing levels of ROS and phosphorylation of p38 MAPK which induced apoptosis. In nude mice bearing JIMT-1 and MCF7 cells xenograft, administration of SP (20 mg/mL in drinking water) significantly suppressed tumor growth by regulating STAT3 and p38 in tumor tissues. These results suggest that SP suppresses proliferation and induces apoptosis in breast cancer cells by inhibiting STAT3, increasing the ROS level and activating p38. Therefore, SP is a candidate therapeutic agent for breast cancer.
Topics: Animals; Antineoplastic Agents; Apoptosis; Autophagy; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; G1 Phase Cell Cycle Checkpoints; Humans; MAP Kinase Signaling System; Mice, Nude; Propionates; Reactive Oxygen Species; Xenograft Model Antitumor Assays; Mice
PubMed: 32973326
DOI: 10.1038/s41401-020-00522-2 -
Animal : An International Journal of... May 2023Most mitigation strategies to reduce enteric methane (CH) production in the rumen induce an excess of rumen dihydrogen (H) that is expelled and consequently not...
Most mitigation strategies to reduce enteric methane (CH) production in the rumen induce an excess of rumen dihydrogen (H) that is expelled and consequently not redirected to the synthesis of metabolites that can be utilised by the ruminant. We hypothesised that phenolic compounds can be potential H acceptors when added to the diet, as they can be degraded to compounds that may be beneficial for the animal, using part of the H available when ruminal methanogenesis is inhibited. We performed four in vitro incubation experiments using rumen inoculum from Murciano-Granadina adult goats: Experiment 1 examined the inhibitory potential of Asparagopsis taxiformis (AT) at different concentrations (0, 1, 2, 3, 4 and 5% of the substrate on a DM basis) in 24 h incubations; Experiment 2 investigated the effect of a wide range of phenolic compounds (phenol, catechol, resorcinol, hydroquinone, pyrogallol, phloroglucinol, gallic acid and formic acid) at different doses (0, 2, 4, and 6 mM) on rumen fermentation for 24 h; Experiment 3 evaluated the combined effect of each phenolic compound at 6 mM with AT at 2% DM in sequential batch cultures for 5 days; and Experiment 4 examined the dose-response effect of phloroglucinol at different concentrations (0, 6, 16, 26 and 36 mM) combined with AT in sequential batch cultures for 5 days. Results from Experiment 1 confirmed that AT at 2% DM substantially inhibited CH production while significantly increasing H accumulation and decreasing the acetate:propionate ratio. Results from Experiment 2 showed that phenolic compounds did not negatively affect rumen fermentation at any dose. In Experiment 3, each phenolic compound at 6 mM combined with AT at 2% DM inhibited CH production. Phloroglucinol numerically decreased H accumulation and significantly increased total gas production (TGP), volatile fatty acid (VFA) production and the acetate:propionate ratio. In Experiment 4, phloroglucinol at increasing doses supplemented with AT at 2% DM significantly decreased H accumulation and the abundances of archaea, protozoa and fungi abundances, and increased TGP, total VFA production and the acetate:propionate ratio in a dose-dependent way. In conclusion, combined treatment with AT and phloroglucinol was successful to mitigate CH production while preventing the accumulation of H, leading to an increase in acetate and total VFA production and therefore an improvement in rumen fermentation in goats.
Topics: Animals; Propionates; Hydrogen; Rumen; Animal Feed; Diet; Fatty Acids, Volatile; Acetates; Phenols; Goats; Phloroglucinol; Fermentation; Methane
PubMed: 37087998
DOI: 10.1016/j.animal.2023.100789 -
PloS One 2015A reference reagent, 3-(trimethylsilyl) propionic-2, 2, 3, 3-d4 acid sodium (TSP), has been used frequently in nuclear magnetic resonance (NMR) and magnetic resonance...
PURPOSE
A reference reagent, 3-(trimethylsilyl) propionic-2, 2, 3, 3-d4 acid sodium (TSP), has been used frequently in nuclear magnetic resonance (NMR) and magnetic resonance spectroscopy (MRS) as an internal reference to identify cell and tissue metabolites, and determine chemical and protein structures. This reference material has been exploited for the quantitative and dynamic analyses of metabolite spectra acquired from cells. The aim of this study was to evaluate the cytotoxicity of TSP on three-dimensionally, agarose gel, cultured cells.
MATERIALS AND METHODS
A human osteosarcoma cell line (MG-63) was selected, and cells were three dimensionally cultured for two weeks in an agarose gel. The culture system contained a mixture of conventional culture medium and various concentrations (0, 1, 3, 5, 7, 10, 20 30 mM) of TSP. A DNA quantification assay was conducted to assess cell proliferation using Quant-iT PicoGreen dsDNA reagent and kit, and cell viability was determined using a LIVE/DEAD Viability/Cytotoxicity kit. Both examinations were performed simultaneously at 1, 3, 7 and 14 days from cell seeding.
RESULTS
In this study, the cytotoxicity of TSP in the 3D culture of MG-63 cells was evaluated by quantifying DNA (cell proliferation) and cell viability. High concentrations of TSP (from 10 to 30 mM) reduced both cell proliferation and viability (to 30% of the control after one week of exposure), but no such effects were found using low concentrations of TSP (0-10 mM).
CONCLUSIONS
This study shows that low concentrations of TSP in 3D cell culture medium can be used for quantitative NMR or MRS examinations for up to two weeks post exposure.
Topics: Cell Line, Tumor; Cell Proliferation; Humans; Osteocytes; Propionates; Trimethylsilyl Compounds
PubMed: 26058017
DOI: 10.1371/journal.pone.0128739 -
Ecotoxicology and Environmental Safety Aug 2022Sodium propionate is widely used as a preservative in food. The widespread use of preservatives is known to cause both environmental and public health problems. This...
Sodium propionate is widely used as a preservative in food. The widespread use of preservatives is known to cause both environmental and public health problems. This study aimed to investigate the effects of sodium propionate on the developmental behavior and glucose metabolism of zebrafish. Our results showed that sodium propionate had no significant effect on the embryonic morphological development of zebrafish embryos but changed the head eye area. Then we found sodium propionate disturbed the thigmotaxis behavior, impaired neural development. Moreover, changes in clock gene expression disrupted the circadian rhythm of zebrafish. Circadian genes regulated insulin sensitivity and secretion in various tissues. Then our results showed that the disorder of circadian rhythm in zebrafish affected glucose metabolism and insulin resistance, which damaged the development of retina. Therefore, the safety of propionate should be further evaluated.
Topics: Animals; Circadian Rhythm; Glucose; Insulin Resistance; Propionates; Zebrafish; Zebrafish Proteins
PubMed: 35753272
DOI: 10.1016/j.ecoenv.2022.113791 -
Journal of Dairy Science Sep 2019The objective of this research was to identify potential short-term metabolic bottlenecks of propionate metabolism in the liver of dairy cows in the postpartum (PP)...
The objective of this research was to identify potential short-term metabolic bottlenecks of propionate metabolism in the liver of dairy cows in the postpartum (PP) period and how such bottlenecks are affected by feeding status. Propionate, produced primarily from the fermentation of starch, decreases dry matter intake for cows in the postpartum period, likely by stimulating oxidation of acetyl-CoA in the liver. In this study, 8 dairy cows [2 blocks of 4 cows each, 6.63 ± 1.19 (mean ± SD) days PP; body condition score of 2.84 ± 0.39] were administered a pulse dose of either 1.5 mol/500 mL of propionic acid (PA) or 500 mL of water (control; CON) to the rumen either 1 h before or 2 h after feeding in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Liver tissue was sampled at -1, 10 and 20 min relative to dosing, and blood was sampled at -30, -20, -10, -1, 5, 10, 15, 20, 25, 30, and 60 min relative to dosing. We hypothesized that rapid propionate absorption results in bottlenecks as enzymes become saturated and cofactors require regeneration. The PA treatment increased plasma propionate and insulin concentrations rapidly, with peaks reached by 5 min regardless of feeding status and cleared from the plasma within 30 min of dosing. The PA treatment decreased plasma nonesterified fatty acid concentration over 30 min compared with CON before but not after feeding. The PA treatment decreased plasma β-hydroxybutyrate concentration and increased plasma lactate concentration compared with CON both before and after feeding. The PA treatment also increased hepatic pyruvate and lactate concentrations compared with CON. The PA treatment tended to increase hepatic isocitrate and fumarate concentrations but did not affect hepatic malate and oxaloacetate concentrations, suggesting that elevated mitochondrial NADH/NAD may have slowed the isocitrate dehydrogenase and fumarase reactions. The PA treatment also increased succinate concentration compared with CON, suggesting that a bottleneck may be present at succinate dehydrogenase. The PA treatment tended to increase citrate concentration despite having no effects on acetyl-CoA or oxaloacetate concentrations. These results are in agreement with our hypothesis that rapid absorption of propionate from the rumen and extraction by the liver results in metabolic bottlenecks in the liver that may affect feeding behavior and dry matter intake in dairy cows in the PP period.
Topics: Animal Feed; Animals; Cattle; Diet; Female; Lactation; Liver; Milk; Postpartum Period; Propionates; Random Allocation; Rumen
PubMed: 31279545
DOI: 10.3168/jds.2018-15907 -
Clinical and Translational Medicine Feb 2022Propionate is a gut microbial metabolite that has been reported to have controversial effects on metabolic health. Here we show that propionate is activated by acyl-CoA...
Propionate is a gut microbial metabolite that has been reported to have controversial effects on metabolic health. Here we show that propionate is activated by acyl-CoA synthetase short-chain family member 3 (ACSS3), located on the mitochondrial inner membrane in brown adipocytes. Knockout of Acss3 gene (Acss3 ) in mice reduces brown adipose tissue (BAT) mass but increases white adipose tissue (WAT) mass, leading to glucose intolerance and insulin resistance that are exacerbated by high-fat diet (HFD). Intriguingly, Acss3 or HFD feeding significantly elevates propionate levels in BAT and serum, and propionate supplementation induces autophagy in cultured brown and white adipocytes. The elevated levels of propionate in Acss3 mice similarly drive adipocyte autophagy, and pharmacological inhibition of autophagy using hydroxychloroquine ameliorates obesity, hepatic steatosis and insulin resistance of the Acss3 mice. These results establish ACSS3 as the key enzyme for propionate metabolism and demonstrate that accumulation of propionate promotes obesity and Type 2 diabetes through triggering adipocyte autophagy.
Topics: Adipocytes, Brown; Adipocytes, White; Adipose Tissue, Brown; Animals; Coenzyme A Ligases; Disease Models, Animal; Mice; Mice, Knockout; Propionates
PubMed: 35184387
DOI: 10.1002/ctm2.665 -
PloS One 2023This study determined the effect of dietary calcium propionate (CaPr) as a source of energy supplementation during the First Half of Gestation (FMG), the Second Half of...
This study determined the effect of dietary calcium propionate (CaPr) as a source of energy supplementation during the First Half of Gestation (FMG), the Second Half of Gestation (SMG), and during All Gestation (AG), on offspring post-weaning growth performance, meat quality, and meat metabolomic profile. Thirty-one pregnant ewes were assigned to one of four treatments: a) supplementation of 30 gd-1 of CaPr during the first half of gestation (day 1 to day 75, n = 8) (FMG); b) supplementation of 30 gd-1 of CaPr during the second half of gestation (day 76 to day 150, n = 8) (SMG); c) supplementation of 30 gd-1 of CaPr during all gestation (AG, n = 8); d) no CaPr supplementation (control; CS, n = 7). The ewes were ad libitum fed a basal diet based on oat hay and corn silage. Ewes were distributed in a completely randomized unbalanced design to four treatments. The FMG group had lower (P ≤ 0.05) birth weight and weaning weight than the CS group. However, the average daily gain was similar across all treatments. Empty body weight and FMG had lower values (P ≤ 0.05) than the other groups. Both FMG and AG had lower hot carcass weight (P ≤ 0.05) compared to CS, while CaPr treatments resulted in reduced hot carcass yield (P ≤ 0.05). Meat color and texture were similar among treatments. A principal component analysis between gestation stages showed a trend for separating CS and FMG from SMG and AG, and that was explained by 93.7% of the data variability (PC1 = 87.9% and PC2 = 5.8%). Regarding meat metabolomic profile, 23 compounds were positively correlated between all treatments. Only 2 were negatively correlated (eicosane and naphthalene 1,2,3); but tetradecanoic acid, hexadecane, undecane 5-methyl, (-)-alpha, hexadecenoic acid, octadecanoic acid, and octadecane had a highly significant correlation (P ≤ 0.05). Overall, dam supplementation with CaPr during different periods of gestation provoked changes in meat metabolites related to the biosynthesis of fatty acids in lambs without negative changes in lamb's growth performance and carcass quality.
Topics: Animals; Female; Pregnancy; Animal Feed; Diet; Dietary Supplements; Meat; Propionates; Sheep
PubMed: 38117821
DOI: 10.1371/journal.pone.0294627 -
Chembiochem : a European Journal of... May 2016Flavin-dependent halogenases are potentially useful biocatalysts for the regioselective halogenation of aromatic compounds. Haloaromatic compounds can be utilised in the...
Flavin-dependent halogenases are potentially useful biocatalysts for the regioselective halogenation of aromatic compounds. Haloaromatic compounds can be utilised in the synthesis and biosynthesis of pharmaceuticals and other valuable products. Here we report the first X-ray crystal structure of a tryptophan 6-halogenase (SttH), which enabled key residues that contribute to the regioselectivity in tryptophan halogenases to be identified. Structure-guided mutagenesis resulted in a triple mutant (L460F/P461E/P462T) that exhibited a complete switch in regioselectivity; with the substrate 3-indolepropionate 75 % 5-chlorination was observed with the mutant in comparison to 90 % 6-chlorination for the wild-type SttH. This is the first clear example of how regiocomplementary halogenases can be created from a single parent enzyme. The biocatalytic repertoire of SttH was also expanded to include a range of indolic and non-indolic substrates.
Topics: Binding Sites; Biocatalysis; Crystallography, X-Ray; Flavin-Adenine Dinucleotide; Halogenation; Indoles; Kinetics; Oxidoreductases; Propionates; Protein Structure, Tertiary; Stereoisomerism; Substrate Specificity
PubMed: 26840773
DOI: 10.1002/cbic.201600051 -
Journal of the American Chemical Society Apr 2019A unique P450 monooxygenase-peroxygenase mutual benefit system was designed as the core element in the construction of a biocatalytic cascade reaction sequence leading...
A unique P450 monooxygenase-peroxygenase mutual benefit system was designed as the core element in the construction of a biocatalytic cascade reaction sequence leading from 3-phenyl propionic acid to ( R)-phenyl glycol. In this system, P450 monooxygenase (P450-BM3) and P450 peroxygenase (OleT) not only function as catalysts for the crucial initial reactions, they also ensure an internal in situ HO recycle mechanism that avoids its accumulation and thus prevents possible toxic effects. By directed evolution of P450-BM3 as the catalyst in the enantioselective epoxidation of the styrene-intermediate, formed from 3-phenyl propionic acid, and the epoxide hydrolase ANEH for final hydrolytic ring opening, ( R)-phenyl glycol and 9 derivatives thereof were synthesized from the respective carboxylic acids in one-pot processes with high enantioselectivity.
Topics: Biocatalysis; Mixed Function Oxygenases; Oxidoreductases; Propionates
PubMed: 30920820
DOI: 10.1021/jacs.9b01939 -
Nutrients Feb 2023Gut microbiota imbalances lead to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is primarily accompanied by hepatic steatosis. Hydroxyphenyl...
Gut microbiota imbalances lead to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is primarily accompanied by hepatic steatosis. Hydroxyphenyl propionic acids (HPP) have shown great potential in inhibiting lipid accumulation but their protective effects concerning NAFLD and intestinal microbiota have remained unclear. In this paper, we investigated the efficacies of 3-HPP and 4-HPP on hepatic steatosis and gut flora in mice fed a high-fat diet (HFD). We found that 3-HPP and 4-HPP administration decreased body weight and liver index, ameliorated dyslipidemia, and alleviated hepatic steatosis. Furthermore, 3-HPP and 4-HPP enhanced the multiformity of gut microbiota; improved the relative abundance of , , and at genus level; increased concentration of acetic acid, propionic acid and butanoic acid in faeces; and reduced systemic endotoxin levels in NAFLD mice. Moreover, 4-HPP upregulated the relative abundance of genera and downregulated the relative abundance of . Furthermore, 3-HPP and 4-HPP regulated lipid metabolism and ameliorated gut dysbiosis in NAFLD mice and 4-HPP was more effective than 3-HPP.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Propionates; Diet, High-Fat; Lipid Metabolism; Liver; Mice, Inbred C57BL
PubMed: 36839401
DOI: 10.3390/nu15041043