scholarly journals Molecular mechanism(s) involved in differential expression of vitamin C transporters along the intestinal tract

2017 ◽  
Vol 312 (4) ◽  
pp. G340-G347 ◽  
Author(s):  
Veedamali S. Subramanian ◽  
Padmanabhan Srinivasan ◽  
Alexis J. Wildman ◽  
Jonathan S. Marchant ◽  
Hamid M. Said

Mammalian cells utilize two transporters for the uptake of ascorbic acid (AA), Na+-dependent vitamin C transporter SVCT-1 and SVCT-2. In the intestine, these transporters are involved in AA absorption and are expressed at the apical and basolateral membrane domains of the polarized epithelia, respectively. Little is known about the differential expression of these two transporters along the anterior-posterior axis of the intestinal tract and the molecular mechanism(s) that dictate this pattern of expression. We used mouse and human intestinal cDNAs to address these issues. The results showed a significantly lower rate of carrier-mediated AA uptake by mouse colon than jejunum. This was associated with a significantly lower level of expression of SVCT-1 and SVCT-2 at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels in the colon than the jejunum, implying the involvement of transcriptional mechanism(s). Similarly, expression levels of SVCT-1 and SVCT-2 mRNA and hnRNA were significantly lower in human colon. We also examined the levels of expression of hepatocyte nuclear factor 1α and specificity protein 1, which drive transcription of the Slc23a1 and Slc23a2 promoters, respectively, and found them to be markedly lower in the colon. Furthermore, significantly lower levels of the activating markers for histone (H3) modifications [H3 trimethylation of lysine 4 (H3K4me3) and H3 triacetylation of lysine 9 (H3K9ac)] were observed in the Slc23a1 and Slc23a2 promoters in the colon. These findings show, for the first time, that SVCT-1 and SVCT-2 are differentially expressed along the intestinal tract and that this pattern of expression is, at least in part, mediated via transcriptional/epigenetic mechanisms. NEW & NOTEWORTHY Our findings show, for the first time, that transporters of the water-soluble vitamin ascorbic acid (i.e., the vitamin C transporters SVCT-1 and SVCT-2) are differentially expressed along the length of the intestinal tract and that the pattern of expression is mediated, at least in part, by transcriptional and epigenetic mechanism(s) affecting both Slc23a1 and Slc23a2 genes.

2016 ◽  
Vol 311 (1) ◽  
pp. C129-C135 ◽  
Author(s):  
Veedamali S. Subramanian ◽  
Padmanabhan Srinivasan ◽  
Hamid M. Said

Vitamin C (ascorbic acid, AA) is indispensable for normal metabolism of all mammalian cells including pancreatic acinar cells (PACs). PACs obtain AA from their surroundings via transport across the cell membrane. Chronic alcohol exposure negatively affects body AA homeostasis; it also inhibits uptake of other micronutrients into PACs, but its effect on AA uptake is not clear. We examined this issue using both in vitro (266-6 cells) and in vivo (mice) models of chronic alcohol exposure. First, we determined the relative expression of the AA transporters 1 and 2 [i.e., sodium-dependent vitamin C transporter-1 (SVCT-1) and SVCT-2] in mouse and human PACs and found SVCT-2 to be the predominant transporter. Chronic exposure of 266-6 cells to alcohol significantly inhibited AA uptake and caused a marked reduction in SVCT-2 expression at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels. Similarly, chronic alcohol feeding of mice significantly inhibited AA uptake and caused a marked reduction in level of expression of the SVCT-2 protein, mRNA, and hnRNA. These findings suggest possible involvement of transcriptional mechanism(s) in mediating chronic alcohol effect on AA uptake by PACs. We also observed significant epigenetic changes (histone modifications) in the Slc23a2 gene (reduction in H3K4me3 level and an increase in H3K27me3 level) in the alcohol-exposed 266-6 cells. These findings show that chronic alcohol exposure inhibits PAC AA uptake and that the effect is mediated, in part, at the level of transcription of the Slc23a2 gene and may involve epigenetic mechanism(s).


2021 ◽  
Vol 64 ◽  
pp. 54-60
Author(s):  
D. R.  Useynov ◽  
E. F. Chelebiev ◽  
О. A. Denisova

The article presents data on the study of the effect of foliar water-soluble mineral fertilizer NOVATEK Solub K-Max 10-5-30 on the biochemical composition and commercial quality of apple fruits. A rise in vitamin C from the introduction of NOVATEK at a rate of 2.5 kg/ha indicates the effectiveness of this drug for optimizing the content of ascorbic acid in fruits. An increase in the content of monosaccharides and a decrease in disaccharides were found for all the studied rates of consumption of agrochemicals. The use of mineral fertilizer “Novatek Solub K-Max” contributed to increase the dry weight of fruits. The application of this mineral fertilizer is recommended for inclusion in the industry regulations for Apple cultivation as one of the elements of the technology. 


Antioxidants ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 96 ◽  
Author(s):  
Giacomo Lazzarino ◽  
Ilaria Listorti ◽  
Gabriele Bilotta ◽  
Talia Capozzolo ◽  
Angela Amorini ◽  
...  

Reactive oxygen species (ROS) are physiologically involved in functions like sperm maturation, capacitation and acrosome reaction, but their excess is involved in male infertility. Antioxidants in seminal plasma (SP) are an important factor balancing physiologic and harmful ROS activities. In this study, we determined and compared the full profiles of the water- and fat-soluble antioxidants in SP and serum of 15 healthy fertile subjects (ranging between the ages of 35 and 42 years). Ejaculates were obtained after 2–5 days of sexual abstinence. After liquefaction and withdrawal of an aliquot for the sperm count, samples were centrifuged to obtain SP. Thirty min after semen donation, a venous blood sample was collected from each subject. Donors with lower SP concentrations of ascorbic acid (n = 5) or α-tocopherol (n = 5) received a 4 week oral administration of either vitamin C (100 mg/day) or vitamin E (30 mg/day). They were then re-assayed to determine the SP and serum levels of ascorbic acid and α-tocopherol. SP and serum samples were properly processed and analyzed by HPLC methods suitable to determine water (ascorbic acid, glutathione (GSH) and uric acid) and fat-soluble (all-trans-retinoic acid, all-trans-retinol, α-tocopherol, carotenoids and coenzyme Q10) antioxidants. Data demonstrate that only ascorbic acid is higher in SP than in serum (SP/serum ratio = 4.97 ± 0.88). The other water-soluble antioxidants are equally distributed in the two fluids (GSH SP/serum ratio = 1.14 ± 0.34; uric acid SP/serum ratio = 0.82 ± 0.12). All fat-soluble antioxidants are about 10 times less concentrated in SP than in serum. In donors treated with vitamin C or vitamin E, ascorbic acid and α-tocopherol significantly increased in both fluids. However, the SP/serum ratio of ascorbic acid was 4.15 ± 0.45 before and 3.27 ± 0.39 after treatment, whilst those of α-tocopherol were 0.11 ± 0.03 before and 0.10 ± 0.02 after treatment. The results of this study, by showing the peculiar composition in water- and fat-soluble antioxidants SP, indicate that it is likely that still-unknown mechanisms allow ascorbic acid accumulation in SP against a concentration gradient. SP mainly relies its defenses on water- rather than fat-soluble antioxidants and on the mechanisms ensuring their transfer from serum.


2019 ◽  
Vol 104 (7) ◽  
pp. e2.58-e2
Author(s):  
Amy-Jo Hooley ◽  
Brandy Cox ◽  
David Devadason ◽  
James Hunter

AimTo assess if routine monitoring of vitamin C in long term parenteral nutrition (PN) patients should be routinely carried out, following a case report of a child with clinical vitamin C deficiency.MethodsVitamin C is an essential water soluble nutrient that cannot be synthesised or stored by humans.1 It is a potent antioxidant with anti-inflammatory and immune- supportive roles,1 Vitamin C levels are depleted in critically ill patients, those with restricted diets, smokers, and those with severe digestive disorders. The stability of micronutrients in PN bags is assumed but rarely confirmed, although a decrease in vitamin C content has been observed when there is a long delay between preparation and packaging.2 The patient, a five year old child stable on long term established full PN presented with a one month gradual reduction in mobility, refusal to weight bear, intermittent temperatures, raised CRP and asymptomatic hypercalcaemia on routine bloods. Investigations included bone profile, vitamin D, and parathyroid hormone levels, and routine sepsis screening. Following the extensive work up for systemic disorders and multiple conversations with orthopaedic and radiology specialists, it was discovered that the patient had bilateral metaphyseal irregularities, which were felt to be in keeping with recognised radiological appearances seen in severe vitamin C deficiency. As a result of this her PN bags were made manufactured and analysed in house quality control laboratory using a method involving UV –vis spectrophotometer to analyse the rate of oxidative decomposition of vitamin C within the bags.ResultsIn the United Kingdom children on long term PN programmes are routinely monitored for selected micronutrient deficiency, but not routinely vitamin C. The vitamin C was increased in the PN to three times the baseline dose for this patient, and a dramatic improvement in the patients symptoms were observed within 5 days, and radiological improvement was noted within 6 weeks after commencing treatment. Unfortunately baseline vitamin C levels were not obtained prior to starting treatment, but levels one month later still showed a significant clinical deficiency. The test bags that were analysed within the laboratory showed that on manufacture the bags contained 48.34 mg/L of ascorbic acid, but by 48 hours this had decreased to 8.5 mg/L.ConclusionVitamin C in PN is at significant risk of degradation by oxidation. Awareness of signs and symptoms of micronutrient deficiency and vigilance of micronutrient deficiencies not routinely measured in children on parenteral nutrition is important. Also more research is required into the oxidation rate of vitamin C in PN to establish how much is required within the PN bag to ensure the recommended daily intake in a PN dependent patient.ReferencesCarr AC, Rosengrave PC, Bayer S, Chambers S, Mehrtens J, Shaw GM. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit Care. 2017;21(1):300. Published 2017 December 11. doi:10.1186/s13054-017-1891-yConroy S, Alsenani A, Sammons H. Factors influencing reported rate of paediatric medication errors. Archives of Disease in Childhood 2014;99:e3. https://adc.bmj.com/content/99/8/e3.19


Author(s):  
Mary K Walingo ◽  

Vitamin C, also known as ascorbic acid, abounds in nature and is highly labile. It is a water-soluble vitamin that is lost in large amounts during food processing. It is a vitamin whose prescribed requirement across cultures is not uniform. For example , the prescribed requirement of vitamin C in Great Britain is 30mg/day, while in the U.S.A., it is 60mg/day and 100mg/day in Japan. These variations are unusual and point to the need for further research to establish the acceptable RDAs for diverse populations. The RDA for vitamin C should be more than the amount needed to prevent the occurrence of disease. Vitamin C plays significant functions in the body that enhance its role in the health status of the human body. The biochemical functions of vitamin C include: stimulation of certain enzymes, collagen biosynthesis, hormonal activation, antioxidant, detoxification of histamine, phagocytic functions of leukocytes, formation of nitrosamine, and proline hydroxylation amongst others. These functions are related to the health effects of vitamin C status in an individual. In human health, vitamin C has been associated with reduction of incidence of cancer, blood pressure, immunity, and drug metabolism and urinary hydroxyproline excretion, tissue regeneration. This vitamin is needed for the proper metabolism of drugs in the body through adequate hepatic mixed function oxidase system. Epidemiological data have revealed the preventive and curative role of vitamin C on certain disease conditions in the body though controversies still persist. Vitamin C is effective in protecting against oxidative damage in tissues and also suppresses formation of carcinogens like nitrosamines. There is an inverse relationship with blood pressure and both plasma vitamin C and Vitamin C. Vitamin C has a lowering effect on blood pressure, especially on systolic pressure more than a diastolic pressure. Low levels of plasma vitamin C are associated with stroke and with an increased risk of all cause mortality. Increased consumption of ascorbic acid raises serum ascorbic levels and could decrease the risk of death.


2001 ◽  
Vol 85 (05) ◽  
pp. 758-760 ◽  
Author(s):  
Roberto Marchioli

SummaryInterest in the use of antioxidants for the treatment of human disease, and in the role of dietary antioxidants in the prevention of disease development, has been sustained for at least two decades. Several anti-oxidant protective mechanisms exist and constitute a primary defensive system including enzymatic defences (glutathione peroxidase and superoxide dismutase, which depend on the presence of ions such as selenium, zinc, copper, and manganese) and naturally occurring vita-mins such as vitamin E, vitamin A, beta-carotene, and vitamin C. The most important natural antioxidants are vitamin E (in the form of α-, β-, γ-, and δ-tocopherols), beta-carotene, vitamin C and selenium (fundamental constituent of glutathione-peroxidase, i.e., an enzyme with antioxidant function). The first two are lipophilic substances whilst ascorbic acid is hydrophilic. Each antioxidant has a different important mechanism of action since oxidative damage can be caused by lipid- or water-soluble molecules. Lipid-soluble antioxidants are likely to be very important in preventing the peroxidation of low-density lipo-proteins (LDL) and this action could be paramount in the prevention of atherosclerosis. On the other hand, water-soluble antioxidants could be useful where a water-soluble oxidative stress occurs (e.g., inflammation). As lipophilic molecules, vitamin E and beta-carotene are incorporated into the LDL particle. Vitamin E is the main lipid-soluble chain-breaking antioxidant in plasma and tissues and converts the peroxyl-free radical to hydroperoxide, a less reactive radical. It acts as a first-line anti-oxidative defence of LDL particles, protecting unsatu-rated fatty acids from peroxidation. Beta-carotene is a carotenoid (precursor of vitamin A, pro-vitamin) that acts as scavenger of oxidising radicals such as singlet oxygen and is a second-line antioxidative defence of LDL cholesterol. Vitamin C (ascorbic acid) can react with singlet oxygen, superoxide, hydroxyl radicals, and is the first line of antioxi-dative defence in water-soluble compartments. In addition, it plays an important role in regenerating reduced -tocopherol.


2017 ◽  
Vol 313 (5) ◽  
pp. G448-G455 ◽  
Author(s):  
Subrata Sabui ◽  
Veedamali S. Subramanian ◽  
Rubina Kapadia ◽  
Hamid M. Said

The essentiality of thiamin stems from its roles as a cofactor [mainly in the form of thiamin pyrophosphate (TPP)] in critical metabolic reactions including oxidative energy metabolism and reduction of cellular oxidative stress. Like other mammalian cells, pancreatic acinar cells (PAC) obtain thiamin from their surroundings and convert it to TPP; mitochondria then take up TPP by a carrier-mediated process that involves the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the MTPP uptake process, but little is known about its possible adaptive regulation. We addressed this issue using pancreatic acinar 266-6 cells (PAC 266-6) maintained under thiamin-deficient (DEF) and oversupplemented (OS) conditions, as well as thiamin-DEF and -OS transgenic mice carrying the SLC25A19 promoter. We found that maintaining PAC 266-6 under the thiamin-DEF condition leads to a significant induction in mitochondrial [3H]TPP uptake, as well as in the level of expression of the MTPPT protein and mRNA compared with thiamin-OS cells. Similar findings were observed in mitochondria from thiamin-DEF mice compared with thiamin-OS. Subsequently, we demonstrated that adaptive regulation of MTTP protein was partly mediated via transcriptional mechanism(s) via studies with PAC 266-6 transfected with the SLC25A19 promoter and transgenic mice carrying the SLC25A19 promoter. This transcriptional regulation appeared to be, at least in part, mediated via epigenetic mechanism(s) involving histone modifications. These studies report, for the first time, that the PAC mitochondrial TPP uptake process is adaptively regulated by the prevailing thiamin level and that this regulation is transcriptionally mediated and involves epigenetic mechanism(s). NEW & NOTEWORTHY Our findings show, for the first time, that the mitochondrial thiamin pyrophosphate (MTPP) uptake process is adaptively regulated by the prevailing thiamin level in pancreatic acinar cells and this regulation is mediated, at least in part, by transcriptional and epigenetic mechanism(s) affecting the SLC25A19 promoter.


Author(s):  
Kazuto Ikemoto ◽  
Shigeki Mori ◽  
Kazuo Mukai

Pyrroloquinoline quinone (PQQ) is a water-soluble quinone compound first identified as a cofactor of alcohol- and glucose-dehydrogenases (ADH and GDH) in bacteria. For example, in the process of ADH reaction, alcohol is oxidized to the corresponding aldehyde, and inversely PQQ is reduced to pyrroloquinoline quinol (PQQH2). PQQ and PQQH2molecules play an important role as a cofactor in ADH and GDH reactions. However, crystal structure analysis has not been performed for PQQ and PQQH2. In the present study, the synthesis of PQQH2powder crystals was performed under air, by utilizing vitamin C as a reducing agent. By reacting a trihydrate of disodium salt of PQQ (PQQNa2·3H2O) with excess vitamin C in H2O at 293 and 343 K, yellowish brown and black powder crystals of PQQH2having different properties were obtained in high yield, respectively. The former was PQQH2trihydrate (PQQH2·3H2O) and the latter was PQQH2anhydrate (PQQH2). Furthermore, sodium-free red PQQ powder crystal (a monohydrate of PQQ, PQQ·H2O) was prepared by the reaction of PQQNa2·3H2O with HCl in H2O. Single crystals of PQQH2and PQQ were prepared from Me2SO/CH3CN mixed solvent, and we have succeeded in the crystal structure analyses of PQQH2and PQQ for the first time.


Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 553
Author(s):  
Maria Bogdan ◽  
Andreea Daniela Meca ◽  
Mihail Virgil Boldeanu ◽  
Dorin Nicolae Gheorghe ◽  
Adina Turcu-Stiolica ◽  
...  

Ascorbic acid (vitamin C) is an important water-soluble vitamin found in many fruits and vegetables. It has well-documented beneficial effects on the human body and is used as a supplement, alone or in combination with other vitamins and minerals. Over recent years, research has focused on possible new therapeutic actions in chronic conditions including periodontal disease (PD). We conducted a systematic review on clinical trials from four databases (PubMed, Clinical Trials, Cochrane, Web of Science) which measured plasmatic/salivary levels of ascorbic acid in PD–diabetes mellitus (DM) association. Six studies were included in our review, three of them analyzing patients with different grades of PD and DM who received vitamin C as a treatment (500 mg vitamin C/day for 2 months and 450 mg/day for 2 weeks) or as part of their alimentation (guava fruits), in combination with standard therapies and procedures. Decreased levels of vitamin C were observed in PD patients with DM but data about efficacy of vitamin C administration are inconclusive. Given the important bidirectional relationship between PD and DM, there is a strong need for more research to assess the positive effects of ascorbic acid supplementation in individuals suffering from both diseases and also its proper regimen for these patients.


2020 ◽  
Vol 25 (4) ◽  
pp. 1-6
Author(s):  
Jwan Abdullmuhsin

Lemon fruit is an important type of Rutaceae family, it has many health benefits due to its important contents. Ascorbic acid (Vitamin C) is a water-soluble vitamin which has reductive properties, so it is used on a large scale as antioxidant in food and drinks. The goal of this search is to determine the concentrations of vitamin C and protein  and minerals (Iron, Magnesium, Potassium , and Calcium) in local and imported lemon juices.Local and imported (from Turkey) lemon were chosen in this study, Ascorbic acid concentration was measured via redox titration method; involve titration with an oxidant solution: dichlorophenol indophenol. Furthermore protein concentration was measured spectrophotometry depending on Biuret method and the minerals by Atomic Absorption Spectrophotometer. The results indicated that local lemon juice is a rich source of vitamin C (24.02±1.07mg/100ml juice) in comparison to the imported lemon. However  the local lemon juice gave a lowest concentration of protein (0.37± 0.21mg/100ml juice). Minerals concentrations were somewhat close when compared between the three studied groups while the pH value was slightly higher in local lemon . Our results indicates that local lemon juice is a highest source of the important antioxidant vitamin (vitamin C) with acceptable acidity .  


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