Intake and putative beneficial effects
Mesembrine - Wikipedia
Polyphenols: food sources and bioavailability
Trehalose is a disaccharide of glucose involved in responses to stress, including oxidative stress, as well as suppression of denatured protein aggregation . Trehalose-6-phosphate synthase (Tps1p) and trehalose-6-phosphate phosphatase (Tps2p) are part of a complex containing also the regulatory proteins Tps3p and Tsl1p, which are co-induced under stress conditions and co-repressed by the glucose regulated Ras-cAMP pathway . Notably, NTH1 gene that encodes a neutral trehalase was also up regulated in cell treated with quercetin. NTH1 is a multiple stress response gene . The simultaneous increase of trehalose hydrolyzing and synthesizing enzymes also occurs during heat stress. This seemingly futile cycling of trehalose turnover during heat stress seems to be necessary for maintenance of a constant glucose concentration in the cytosol and for cellular recovery from stress , .
In a previous study, the analysis of cellular protection against oxidative stress in yeast exposed to quercetin for different time periods showed that a 15 min pre-treatment was sufficient to increase hydrogen peroxide resistance . Aiming to characterize short-term adaptive responses triggered by quercetin and to identify cellular functions that may contribute to its protective effect against oxidative stress, changes in gene expression were analyzed by using microarrays. S. cerevisiae cells were treated with 300 µM quercetin or dimethyl sulphoxide (DMSO; control cells) during 15 min and mRNA was isolated by the hot phenol method, as described in . The microarray analysis showed that treatment with quercetin led to an increase of the mRNA levels of 221 genes, whereas that of 613 genes was diminished (see supplementary and ). Genes differentially expressed were sorted into functional categories according to MIPS (Munich Information Center for Protein Sequences). Genes associated with transcription (22%), protein fate (18%), cell transport (15%), cell cycle and DNA processing (14%), metabolism (13%), biogenesis of cellular components (13%) and protein synthesis (10%) were down regulated, whereas genes related with metabolism (39%), protein fate (24%), cell transport (24%), biogenesis of cellular components (18%) and cell rescue and defense (16%) were up regulated by quercetin treatment ().
» Future Issue | Pakistan Journal of Pharmaceutical …
To validate the microarray data, the expression of five genes was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Four of these genes were up regulated in the microarray analysis and are functionally related with the metabolism of carbohydrates, including glycogen and trehalose (whose levels were also measured; see below): HXK1 (Hexokinase isoenzyme 1, which catalyses phosphorylation of glucose; its expression is highest during growth on non-glucose carbon sources), GPH1 (glycogen phosphorylase), TPS1 (synthase subunit of trehalose-6-phosphate synthase/phosphatase complex, which synthesizes trehalose) and TSL1 (subunit of trehalose 6-phosphate synthase/phosphatase complex). The expression of RPB5 (RNA polymerase subunit), which was down regulated in the microarray analysis, was also assessed by RT-qPCR. The mRNA levels were normalized to ACT1 (encodes for actin; internal control) and RPS6A (a second control that was chosen based on the fact that its expression was not altered by quercetin, according to the microarray data). The results obtained showed a correlation between microarray and RT-qPCR data ().
Changes in expression of genes related to glycogen and trehalose metabolism led us to measure the levels of these reserve carbohydrates. The results obtained show that glycogen levels decreased approximately 4-fold whereas trehalose levels increased 4-fold upon quercetin-treatment (). Overall, the gene expression results and the carbohydrate levels suggest that glycogen is metabolized to provide glucose for trehalose biosynthesis. Moreover, the protective effect of quercetin against H2O2 decreased in tps1Δ cells (): in the presence of this polyphenol, oxidative stress resistance increased 2.5-fold and 1.5-fold in wild type and tps1Δ cells, respectively. This suggests that trehalose production contributes to quercetin-induced H2O2 resistance.
Click on the article to view it
In conclusion, this study shows that quercetin treatment mimics glucose restriction and modulates carbohydrate metabolism in favor of the biosynthesis of trehalose, a disaccharide with antioxidant properties. Moreover, the activation of the CWI pathway in yeast contributes to the xenohormetic activity of quercetin. The overall results suggest that quercetin exerts protective effects through the modulation of cell signaling pathways.
Notably, quercetin induced several genes belonging to carbohydrate metabolism, including metabolism of energy reserves, known to be repressed by glucose. Specifically, quercetin up regulated genes associated with gluconeogenesis, glycogenolysis, glucose uptake and trehalose biosynthesis, as well as IRA1 and IRA2 genes, which encode GTPase-activating proteins that negatively regulate the glucose-activated cAMP-dependent protein kinase signaling pathway . These metabolic alterations redirect carbohydrate metabolism towards the production of trehalose, whose levels increased 4-fold after exposure to quercetin. Trehalose-6-phosphate, one of the intermediates of this pathway, and Tps1p play a major role in restricting glucose influx into glycolysis . Trehalose is a disaccharide of glucose with stress-protectant functions . Our results indicate that the increase in trehalose production contributes to oxidative stress resistance of cells treated with quercetin, since inactivation of TPS1 gene decreased its protective effect. Interestingly, glycogen levels also decrease whereas trehalose levels remain unchanged in stationary phase (quiescent) cells, which display a high oxidative stress resistance phenotype. Under these conditions, trehalose also functions as an energy reserve used by yeast cells upon exit from the quiescent state .
Nutrients | July 2017 - Browse Articles
Nutrients, an international, peer-reviewed Open Access journal.
Flavones - Wikipedia
Antibiotic-Resistant Bugs in the 21st Century — A …
Citation data is made available by participants in Crossref's Cited-by Linking service.
Mycoplasmas - Stealth Pathogens
methional 3268-49-3 - The Good Scents Company
Gastrointestinal Toxicity of Nonsteroidal …
Oxidative stress has been implicated in aging and age-related diseases. Mounting evidence suggests that natural compounds with antioxidant properties exert health beneficial effects. The antioxidant activities of polyphenols have been attributed to ROS scavenging. However, a number of recent studies suggest that they also act through modulation of cell signaling pathways that increase cellular defense mechanisms. This phenomenon, known as xenohormesis, refers to sensing in one organism (yeast in this study) of a compound produced in another specie (plant) in response to environmental stress, leading to the induction of a defense response that increases its chances of survival . We have previously shown that quercetin, the most common flavonol in the diet, increases oxidative stress resistance in yeast cells by scavenging free radicals, maintaining the redox homeostasis, and preventing protein carbonylation and lipid peroxidation . Aiming to characterize genome-wide changes in gene expression induced by quercetin in yeast, a microarray analysis was performed. The results obtained show that quercetin down regulated a significant number of genes belonging to RNA metabolism and ribosome biogenesis categories. This cellular adaptation has been observed in response to multiple stress conditions and is beneficial since it spares energy resources for cellular processes other than ribosome biosynthesis (the most energy consuming cellular process).
"I have always been impressed by the quick turnaround and your thoroughness. Easily the most professional essay writing service on the web."
"Your assistance and the first class service is much appreciated. My essay reads so well and without your help I'm sure I would have been marked down again on grammar and syntax."
"Thanks again for your excellent work with my assignments. No doubts you're true experts at what you do and very approachable."
"Very professional, cheap and friendly service. Thanks for writing two important essays for me, I wouldn't have written it myself because of the tight deadline."
"Thanks for your cautious eye, attention to detail and overall superb service. Thanks to you, now I am confident that I can submit my term paper on time."
"Thank you for the GREAT work you have done. Just wanted to tell that I'm very happy with my essay and will get back with more assignments soon."