Purpose: Epidemiological and intervention studies have attempted to link the health effects of a diet rich in fruits and vegetables with the consumption of polyphenols and their impact in neurodegenerative diseases. Studies have shown that polyphenols can cross the intestinal barrier and reach concentrations in the bloodstream able to exert effects in vivo. However, the effective uptake of polyphenols in the brain is still regarded with some reservations. Here we describe a combination of approaches to examine the putative transport of blackberry-digested polyphenols (BDP) across the blood-brain barrier (BBB) and ultimate evaluation of their beneficial effects.
Blood-brain barrier transport and neuroprotective potential of blackberry-digested polyphenols: an in vitro study.
Sex, Specimen part, Cell line, Race
View SamplesWe used old (~96-102 weeks of age) and young (~28-34 weeks of age) rats from HCR and LCR generations 29 and 32, respectively. The study included eight groups; HCR-Old-Exhausted (H-O-E, n=6), HCR-Old-Rest (H-O-R, n=6), HCR-Young-Exhausted (H-Y-E, n=6), HCR- Young -Rest (H-Y-R, n=6), LCR-Old-Exhausted (L-O-E, n=6), LCR-Old-Rest (L-O-R, n=6), LCR-Young-Exhausted (L-Y-E, n=6), and LCR- Young -Rest (L-Y-R, n=6). For the exhausted rats, dissections were performed within 10 min after the maximal running distance was reached.
Selection-, age-, and exercise-dependence of skeletal muscle gene expression patterns in a rat model of metabolic fitness.
Specimen part
View SamplesPlants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as collateral damage to other cellular components and therefore are not expected to provoke identical responses by the cell.
High atomic weight, high-energy radiation (HZE) induces transcriptional responses shared with conventional stresses in addition to a core "DSB" response specific to clastogenic treatments.
Age, Time
View SamplesIron is an essential trace element whose absorption is usually tightly regulated in the duodenum. HFE-related hereditary hemochromatosis (HH) is characterized by abnormally low expression of the iron-regulatory hormone, hepcidin, which results in increased iron absorption. The liver is crucial for iron homeostasis as it is the main production site of hepcidin. The aim of this study was to explore and compare the genome-wide transcriptome response to Hfe deficiency and dietary iron overload in murine liver and duodenum.
Global transcriptional response to Hfe deficiency and dietary iron overload in mouse liver and duodenum.
Sex, Age, Specimen part
View SamplesThe heart uses primarily fatty acids and glucose for deriving energy. The majority of energy in the healthy heart derives from fat utilization, with the remainder coming primarily from the catabolism of glucose. Classical studies by Randle and colleagues describe the ability of the heart to switch its mode of utilization facilely and reversibly between glucose and fatty acids (myocardial glucose-fatty acid cycle or Randle cycle). However, under conditions of pathological stress, reliance of the heart on fatty acids decreases with a concomitant increase in reliance on glucose. It is unclear how such changes in metabolism regulate gene expression in the heart. Therefore, we examined how regulation of glycolysis at the level of phosphofructokinase modulates gene expression in the heart. We performed transcriptomic analysis of hearts from mice expressing either kinase-deficient phosphofructokinase 2 (GlycoLo) or phosphatase-deficient phosphofructokinase 2 (GlycoHi) under the control of the -MHC promoter, which restricted expression of the transgenes to the heart. Phosphofructokinase 2 only controls the ability of the myocyte to regulate abundance of a single metabolite, F-2,6-P2, which is an allosteric regulator of the rate-limiting and committed step in glycolysis. Parallel radiometric and metabolomic studies showed the expected increases or decreases in glycolytic flux along with diametrically opposite changes in fat metabolism, which is consistent with the myocardial glucose-fatty acid cycle. Transcriptomic analyses showed remarkable changes in gene transcription in these hearts, which indicates that glucose and/or fatty acid metabolism is a driver of transcriptional programs in the heart. Furthermore, glycolytic activity coordinately regulated numerous genes in the heart, including genes important for cardiac remodeling as well as genes regulating gluconeogenic and ancillary biosynthetic pathway activity. These findings reveal that glycolytic rate is a critical regulator of gene expression in the heart and can coordinate programs that modulate cardiac metabolism, growth, and hypertrophy.
Exercise-Induced Changes in Glucose Metabolism Promote Physiological Cardiac Growth.
Sex, Age, Specimen part
View SamplesMelphalan-induced modulation of miR-221/222 levels in MM cells. Melphalan-resistant U266/LR7 cells showed the highest induction of miR-221/222 after drug exposure. To study the transcriptome perturbation induced in MM cells following the combination of miR-221/222 inhibitors plus melphalan we used the whole gene expression data
A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype.
Sex
View SamplesThe molecular pathways which are activated and contribute to physiological remodeling of skeletal muscle in response to endurance exercise have not been fully characterized. We previously reported that ~800 gene transcripts are regulated following 6 weeks of supervised endurance training in young sedentary males, referred to as the training responsive transcriptome (TRT). Here we utilized this database together with data on biological variation in muscle adaptation to aerobic endurance training in both humans and a novel out-bred rodent model to study the potential regulatory molecules that coordinate this complex network of genes. We identified three DNA sequences representing RUNX1, SOX9, and PAX3 transcription factor binding sites as over-represented in the TRT. In turn, miRNA profiling indicated that several miRNAs targeting RUNX1, SOX9 and PAX3 were down-regulated by endurance training. The TRT was then examined by contrasting subjects who demonstrated the least vs. the greatest improvement in aerobic capacity (low vs. high responders), and at least 100 of the 800 TRT genes were differentially regulated, thus suggesting regulation of these genes may be important for improving aerobic capacity. In high responders, pro-angiogenic and tissue developmental networks emerged as key candidates for coordinating tissue aerobic adaptation. Beyond RNA level validation there were several DNA variants that associated with VO(2)max trainability in the HERITAGE Family Study but these did not pass conservative Bonferroni adjustment. In addition, in a rat model selected across 10 generations for high aerobic training responsiveness, we found that both the TRT and a homologous subset of the human high responder genes were regulated to a greater degree in high responder rodent skeletal muscle. This analysis provides a comprehensive map of the transcriptomic features important for aerobic exercise-induced improvements in maximal oxygen consumption.
A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype.
Sex
View SamplesPurpose: Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and soleus gene expression we examined genome-wide gene expression in soleus muscle of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in man, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in the two groups, since accumulating evidence indicates that exercise has profound beneficial effects on the metabolic syndrome.
Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO2max.
No sample metadata fields
View SamplesAerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between aerobic capacity and cardiac gene expression we examined genome-wide gene expression in hearts of rats artificially selected for high- and low running capacity (HCR and LCR, respectively) over 16 generations. HCR were born with an athletic phenotype, whereas LCR exhibited features of the metabolic syndrome.
Aerobic capacity-dependent differences in cardiac gene expression.
Sex
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