The effect of molybdenum on ascorbic acid metabolism in rats.
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ABSTRACT:
SUBMITTER: Sasmal N
PROVIDER: S-EPMC1198553 | biostudies-other | 1968 Feb
REPOSITORIES: biostudies-other
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Project description:1. d-Glucuronolactone reductase, l-gulonolactone oxidase, uronolactonase, dehydroascorbatase, l-gulonate dehydrogenase and l-gulonate decarboxylase have been measured in the tissues of rats fed on diets containing variable amounts of protein. Rats fed on a protein-free or a 2% casein diet for 15 days showed a marked decline in the activities of d-glucuronolactone reductase, l-gulonolactone oxidase, uronolactonase and dehydroascorbatase in the liver, and no change in l-gulonate dehydrogenase and l-gulonate decarboxylase activities in the kidney when compared with rats fed on diets containing 9%, 18% or 25% casein. Giving diets containing 60% or 88% casein to rats did not appreciably alter the activities of uronolactonase, dehydroascorbatase, l-gulonate dehydrogenase and l-gulonate decarboxylase, but inhibited considerably the activities of d-glucuronolactone reductase and l-gulonolactone oxidase in the liver, resulting in decreased synthesis of ascorbic acid. 2. Rats fed on a 25% casein diet showed maximal weight gain, higher tissue reserve of ascorbic acid and higher urinary excretion of both ascorbic acid and glucuronic acid when compared with rats fed on diets containing lower or higher amounts of protein.
| S-EPMC1198552 | biostudies-other
Project description:To elucidate metabolism of ascorbic acid (AsA) in sweet cherry fruit (Prunus avium 'Hongdeng'), we quantified AsA concentration, cloned sequences involved in AsA metabolism and investigated their mRNA expression levels, and determined the activity levels of selected enzymes during fruit development and maturation. We found that AsA concentration was highest at the petal-fall period (0 days after anthesis) and decreased progressively during ripening, but with a slight increase at maturity. AsA did nevertheless continue to accumulate over time because of the increase in fruit fresh weight. Full-length cDNAs of 10 genes involved in the L-galactose pathway of AsA biosynthesis and 10 involved in recycling were obtained. Gene expression patterns of GDP-L-galactose phosphorylase (GGP2), L-galactono-1, 4-lactone dehydrogenase (GalLDH), ascorbate peroxidase (APX3), ascorbate oxidase (AO2), glutathione reductase (GR1), and dehydroascorbate reductase (DHAR1) were in accordance with the AsA concentration pattern during fruit development, indicating that genes involved in ascorbic acid biosynthesis, degradation, and recycling worked in concert to regulate ascorbic acid accumulation in sweet cherry fruit.
| S-EPMC5330498 | biostudies-literature
Project description:BACKGROUND:Mesenchymal stem cells (MSCs) are multipotent cells holding much promise for applications in regenerative medicine. However, with problems such as aging, increases in heteroploid cells, genomic instability, and reduced maintenance of stemness, more stable culturing methods and the production of MSCs with an improved therapeutic effect are desired. Ascorbic acid (AsA), which is a cofactor for a variety of enzymes and has an antioxidant effect, cannot be synthesized by certain animals, including humans. Nevertheless, little attention has been paid to AsA when culturing MSCs. METHODS:We analyzed the effect of adding AsA to the culture medium on the proliferation and metabolism of human MSCs by serial analysis of gene expression and metabolome analysis. RESULTS:We found that AsA promotes MSC proliferation, and is particularly useful when expanding MSCs isolated from bone marrow. Serial analysis of gene expression and metabolome analysis suggested that, due to HIF1α accumulation caused by decreased activity of the enzymes that use AsA as a coenzyme in cultures without AsA, genes downstream of HIF1α are expressed and there is a conversion to a hypoxia-mimetic metabolism. AsA promotes HIF1α breakdown and activates mitochondria, affecting cell proliferation and metabolism. Comprehensive evaluation of the effects of AsA on various metabolic products in MSCs revealed that AsA increases HIF1α hydroxylase activity, suppressing HIF1a transcription and leading to mitochondrial activation. CONCLUSIONS:Adding AsA during MSC expansion leads to more efficient preparation of cells. These are expected to be important findings for the future application of MSCs in regenerative medicine.
| S-EPMC5889584 | biostudies-literature
Project description:Ascorbic acid (AA) is a powerful antioxidant and play as a cofactor for various enzymes in vivo. In this study, we investigated the effect of AA depletion on gene expression in the liver and lipid metabolism by using SMP30/GNL knockout (KO) mice which are unable to biosynthesis AA. First, we performed microarray analysis. Briefly, SMP30/GNL KO mice were weaned and divided into two groups; AA-depleted and supplemented groups, which mice were free access to water containing 1.5 g/L AA. After 4 weeks, mRNA was isolated and purified from the liver. In this study, Affymetrix® GeneChip® was used for microarray analysis. Actually, AA-depletion altered many gene expressions related to lipid metabolism. Especially, Cytochrome P450 7a1 (Cyp7a1), a late-limiting enzyme of bile acid biosynthesis, gene expression was significantly up-regulated. We also confirmed Cyp7a1 protein levels by Western blotting. Next, we investigated the influence of AA depletion on lipid metabolism. We examined the lipid and bile acid levels in the liver, plasma, and gallbladder from SMP30/GNL KO mice. Amount of total bile acid (TBA), free fatty acid (FA), total cholesterol (TC), triglyceride (TG), and phospholipids (PL) were measured by colorimetric method. AA depletion reduced TBA levels in the liver and gallbladder. However, FA, TC, TG, and PL in the plasma and liver were not changed by AA depletion. Although Cyp7a1 gene expression and protein levels were increased by AA depletion, amount of bile acid were reduced. Conclusively, we have shown that AA depletion reduced bile acid biosynthesis and elevated Cyp7a1 gene expression and protein levels. Thus, AA is an essential for bile acid biosynthesis pathway.
2015-10-04 | GSE41365 | GEO
Project description:Several amidated biologically active peptides such as pancreastatin, thyrotropin-releasing hormone, pancreatic polypeptide and amylin are produced in endocrine pancreatic tissue which contains the enzyme necessary for their final processing, i.e. peptidylglycine alpha-amidating mono-oxygenase (EC 1.14.17.3). The enzyme needs ascorbic acid for activity as well as copper and molecular oxygen. The present work shows that pancreatic islet cells prepared from overnight cultures of isolated islets from 5-7-day-old rats accumulate 14C-labelled ascorbic acid by a Na(+)-dependent active transport mechanism which involves a saturable process (estimated Km 17.6 microM). Transport was inhibited by ouabain, phloridzin, cytochalasin B, amiloride and probenecid. Glucose inhibited or stimulated uptake, depending on the length of incubation time of the cells. The uptake of dehydroascorbic acid was linearly dependent on concentration. Dehydroascorbic acid was converted to ascorbic acid by an unknown mechanism after uptake. The uptake of both ascorbic acid and dehydroascorbic acid was inhibited by tri-iodothyronine, and uptake of ascorbic acid, but not of dehydroascorbic acid, was inhibited by glucocorticoids. Isolated secretory granules contained a fairly low concentration of iron but a high concentration of copper.
| S-EPMC1149973 | biostudies-other
Project description:Nephrotoxicity is a dose-limiting factor of colistin, a last-line therapy for multidrug-resistant Gram-negative bacterial infections. An earlier animal study revealed a protective effect of ascorbic acid against colistin-induced nephrotoxicity. The present randomized controlled study was conducted in 28 patients and aimed to investigate the potential nephroprotective effect of intravenous ascorbic acid (2 g every 12 h) against colistin-associated nephrotoxicity in patients requiring intravenous colistin. Thirteen patients received colistin plus ascorbic acid, whereas 15 received colistin alone. Nephrotoxicity was defined by the RIFLE classification system. Additionally, urinary neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-beta-d-glucosaminidase (NAG) were measured as markers of renal damage, and plasma colistin concentrations were quantified. The baseline characteristics, clinical features, and concomitant treatments of the patients in the two groups were comparable. The incidences of nephrotoxicity were 53.8% (7/13) and 60.0% (9/15) in the colistin-ascorbic acid group and the colistin group, respectively (P = 0.956; relative risk [RR], 0.9; 95% confidence interval, 0.47 to 1.72). In both groups, the urinary excretion rates of NGAL and NAG on day 3 or 5 of colistin treatment and at the end of colistin treatment were significantly higher than those at the respective baselines (P < 0.05). However, the urinary excretion rates of these biomarkers at the various times during colistin treatment did not differ significantly between the groups (P > 0.05). The plasma colistin concentrations in the two groups were not significantly different (P > 0.28). The clinical and microbiological outcomes and mortality of the patients in the two groups were not significantly different. This preliminary study suggests that ascorbic acid does not offer a nephroprotective effect for patients receiving intravenous colistin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01501968.).
| S-EPMC4432219 | biostudies-literature
Project description:Proximal femur fractures show a high prevalence in elderly patients and are associated with an elevated risk of multimorbidity and early mortality. Recovery is impaired by malnutrition and oxidative stress, which is affected by antioxidants such as ascorbic acid (AA). This study monitored AA levels during hospitalization of patients with a proximal femur to investigate the influence of AA status to the clinical outcome. AA levels of 25 elderly patients with a proximal femur fracture were measured during hospitalization using high performance liquid chromatography. Plasma samples were collected preoperatively, on the first day after surgery, on the third day after surgery and on the day of discharge. Nutritional Risk Screening 2002 (NRS) and Mini Nutritional Assessment (MNA) were assessed to evaluate the nutritional status. In patients with proximal femoral fractures, preoperative AA concentrations were significantly lower compared to elderly patients without an acute fracture. A significant decrease of 33.8% in AA plasma level was measured on the day after surgery with a significant recovery up to the time of discharge. The preoperative AA status did not have any significant effect on clinical outcome. However, inadequate AA levels (<50 µmol/L) upon discharge significantly increased the incidence and the severity of postoperative complications. These results indicate that the AA status upon discharge has a greater impact on clinical outcome than assumed, and therefore, AA supplementation during hospitalization should be considered.
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Project description:We studied the effects of various assay temperatures, representing hypothermia (25°C), normothermia (35°C), and hyperthermia (42°C), on the oxidation of lipid-derived fuels in rat skeletal muscle mitochondria of untrained and endurance-trained rats. Adult 4-month-old male Wistar rats were assigned to a training group (rats trained on a treadmill for 8 weeks) or a sedentary control group. In skeletal muscle mitochondria of both control and trained rats, an increase in the assay temperature from 25°C to 42°C was accompanied by a consistent increase in the oxidation of palmitoylcarnitine and glycerol-3-phosphate. Moreover, endurance training increased mitochondrial capacity to oxidize the lipid-derived fuels at all studied temperatures. The endurance training-induced increase in mitochondrial capacity to oxidize fatty acids was accompanied by an enhancement of mitochondrial biogenesis, as shown by the elevated expression levels of Nrf2, PGC1?, and mitochondrial marker and by the elevated expression levels of mitochondrial proteins involved in fatty acid metabolism, such as fatty acid transporter CD36, carnitine palmitoyltransferase 1A (CPT1A), and acyl-CoA dehydrogenase (ACADS). We conclude that hyperthermia enhances but hypothermia attenuates the rate of the oxidation of fatty acids and glycerol-3-phosphate in rat skeletal muscle mitochondria isolated from both untrained and trained rats. Moreover, our results indicate that endurance training up-regulates mitochondrial biogenesis markers, lipid-sustained oxidative capacity, and CD36 and CPT1A proteins involved in fatty acid transport, possibly via PGC1? and Nrf2 signaling pathways.
| S-EPMC5726737 | biostudies-literature
Project description:A comprehensive investigation of abscisic acid (ABA) biosynthesis and its influence on other important phytochemicals is critical for understanding the versatile roles that ABA plays during strawberry fruit ripening. Using RNA-seq technology, we sampled strawberry fruit in response to ABA or nordihydroguaiaretic acid (NDGA; an ABA biosynthesis blocker) treatment during ripening and assessed the expression changes of genes involved in the metabolism of pigments, ascorbic acid (AsA) and folic acid in the receptacles. The transcriptome analysis identified a lot of genes differentially expressed in response to ABA or NDGA treatment. In particular, genes in the anthocyanin biosynthesis pathway were actively regulated by ABA, with the exception of the gene encoding cinnamate 4-hydroxylase. Chlorophyll degradation was accelerated by ABA mainly owing to the higher expression of gene encoding pheide a oxygenase. The decrease of β-carotene content was accelerated by ABA treatment and delayed by NDGA. A high negative correlation rate was found between ABA and β-carotene content, indicating the importance of the requirement for ABA synthesis during fruit ripening. In addition, evaluation on the folate biosynthetic pathway indicate that ABA might have minor function in this nutrient's biosynthesis process, however, it might be involved in its homeostasis. Surprisingly, though AsA content accumulated during fruit ripening, expressions of genes involved in its biosynthesis in the receptacles were significantly lower in ABA-treated fruits. This transcriptome analysis expands our understanding of ABA's role in phytochemical metabolism during strawberry fruit ripening and the regulatory mechanisms of ABA on these pathways were discussed. Our study provides a wealth of genetic information in the metabolism pathways and may be helpful for molecular manipulation in the future.
| S-EPMC4460069 | biostudies-literature
Project description:In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucose and lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in humans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glucose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and increased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glucose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no significant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P<0.001) in 24-hour fecal BA excretion on post-operative day 3 compared to ZDF-SHAM, which paralleled a significant increase in plasma PYY. Ratios of plasma and fecal cholic acid/chenodeoxycholic acid derived BAs were decreased in RYGB groups. In addition, tissue mRNA expression analysis suggested early intestinal BA reabsorption and potentially reduced hepatic cholic acid production in RYGB groups. In summary, we present novel data on RYGB-mediated changes in BA metabolism to further understand the role of BAs in RYGB-induced metabolic effects in humans.
| S-EPMC4370587 | biostudies-literature