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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin C plays an important role in embryogenesis and fetal growth as well as in the progression of pregnancy and delivery. Therefore, it is important to understand the mechanism that mediates its transport to the fetus as well as the possible influences by endogenous and exogenous substances on its placental uptake. The aim of this study was to investigate placental sodium-dependent vitamin C transporters (SVCT) 1 and 2. By means of RT-PCR, we found that SVCT2, but not SVCT1, mRNA is expressed in human trophoblast cell line HTR-8/SVneo. Our method was able to confirm SVCT2 mRNA expression in human first-trimester chorionic villi but not in term placental tissue. Cell line kinetic studies of [(14)C] ascorbic acid (AA) uptake indicated a one-site model and a saturable process. Fetal bovine serum (FBS) and epidermal growth factor (EGF) do not influence the transport properties, although they significantly increase the expression of SVCT2. Steroid hormones (17beta-estradiol, progesterone and cortisol), flavonoids (genistein and quercetin) and non-steroidal anti-inflammatory drugs (NSAIDs) (indomethacin and diclofenac) inhibit [(14)C]AA uptake in a dose-dependent and non-competitive manner. On the contrary, the process is not influenced by aspirin. Our study suggests the use of HTR-8/SVneo cells as a suitable model for trophoblast vitamin C transport investigation.
Mol Hum Reprod 2007 Jan
PMID:Expression and characterization of vitamin C transporter in the human trophoblast cell line HTR-8/SVneo: effect of steroids, flavonoids and NSAIDs. 1709 84

The characteristics of vitamin C (ascorbic acid, ASC) transport were studied in polarized cultured monolayers of the chick (Gallus gallus) renal proximal tubule in Ussing chambers. Under voltage clamp conditions, monolayers responded to apical addition of ASC in a dose-dependent manner, with positive short circuit currents (I(SC)), ranging from 3 microA/cm(2) at 5 microM ASC to a maximal response of 27 microA/cm(2) at 200 microM, and a half-maximal response at 40 microM. There was no effect of basolateral addition of ASC, indicating a polarized transport process. The oxidized form of ASC, dehydroascorbic acid had negligible effects. The I(SC) response to ASC was completely eliminated with Na(+) ion replacement, and was also eliminated by bilateral reduction of bath Cl(-), from 137 to 2.6 mM. There was significant inhibition of the I(SC) responses to 30 microM ASC by the flavanoid quercetin (50 microM) and by 100 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 5-ethylisopropylamiloride (EIPA), blockers of anion exchangers and sodium-proton exchangers, respectively. There was no inhibition, however, by the chloride channel blocker 5-nitro-2(3-phenylpropylamino)benzoic acid (NPPB). Phorbol 12-myristate 13 acetate (PMA), the phorbol ester activator of protein kinase C, caused a 37% decrease in the I(SC) response to ASC. Chicken-specific primers to an EST homolog of the human vitamin C transporter SVCT1 (SLC23A1) were designed and used to probe transporter expression in these cells. RT-PCR analysis demonstrated the presence of chicken SVCT1 in both cultured cells and in freshly isolated proximal tubule fragments. These data indicate the presence of an electrogenic, sodium-dependent vitamin C transporter (SVCT1) in the chick renal proximal tubule. Vitamin C transport and conservation by the kidney is likely to be especially critical in birds, due to high plasma glucose levels and resulting high levels of reactive oxygen species.
Comp Biochem Physiol A Mol Integr Physiol 2007 Mar
PMID:Vitamin C transport and SVCT1 transporter expression in chick renal proximal tubule cells in culture. 1725 85

The reduced form of vitamin C, ascorbic acid, is well known for its function as an antioxidant and as a protective agent against scurvy. However, many recent studies indicate other functions for vitamin C in mammalian cells. Novel findings provide possible explanations for observed beneficial effects of a high intake of vitamin C on cell growth, gene transcription, host resistance to infection, uptake of polyamines and clearance of misfolded proteins. Vitamin C exerts its effects indirectly via hypoxia-inducible factor, nitric oxide synthase and the heparan sulfate proteoglycan glypican-1, which is deglycanated in a vitamin C- and copper-dependent reaction.
Trends Mol Med 2007 Apr
PMID:Novel aspects of vitamin C: how important is glypican-1 recycling? 1734 97

Bioactivation of nitroglycerin (GTN) into an activator of soluble guanylate cyclase (sGC) is essential for the vasorelaxant effect of the drug. Besides several enzymes that catalyze GTN bioactivation, the reaction with cysteine is the sole nonenzymatic mechanism known so far. Here we show that a reaction with ascorbate results in GTN bioactivation. In the absence of ascorbate, GTN did not affect the activity of purified sGC. However, the enzyme was activated to approximately 20% of maximal NO-stimulated activity by GTN in the presence of 10 mM ascorbate with an EC(50) value of 27.3 +/- 4.9 microM GTN. The EC(50) value of ascorbate was 0.11 +/- 0.011 mM. Activation of sGC was sensitive to oxyhemoglobin, superoxide, and a heme-site enzyme inhibitor. GTN had no effect when ascorbate was replaced by 1000 U of superoxide dismutase per milliliter. Ascorbate is known to reduce inorganic nitrite to NO. In the presence of 10 mM ascorbate, approximately 30 microM nitrite caused the same increase in sGC activity as 0.3 mM GTN. Determination of ascorbate-driven 1,2- and 1,3-glycerol dinitrate formation indicated that a 140 nM concentration of products was generated from 0.3 mM GTN within 10 min, excluding nitrite as a relevant intermediate. Our results suggest that a reaction between GTN and ascorbate or an ascorbate-derived species yields an activator of sGC with NO-like chemical properties. This reaction may contribute to GTN bioactivation in blood vessels under conditions of GTN tolerance and ascorbate supplementation.
Mol Pharmacol 2007 Jul
PMID:Bioactivation of nitroglycerin by ascorbate. 1744 67

The results of several experimental studies have shown that ascorbic acid inhibits tumor growth and metastasis. Ascorbic acid is an antioxidant that acts as a scavenger for a wide range of reactive oxygen species (ROS). Both tumour metastasis and cell migration have been correlated with the intracellular ROS level, so it was postulated that the inhibitory effect of ascorbic acid derivatives on cell motility may be caused by scavenging of ROS. Time-lapse analyses of Walker 256 carcinosarcoma cell migration showed that both the speed of movement and the cell displacement were inhibited by ascorbic acid applied in concentrations ranging from 10 to 250 microM. This effect correlated with a reduction in the intracellular ROS level in WC 256 cells, suggesting that ROS scavenging may be a mechanism responsible for the inhibition of WC 256 cell migration. However, another potent antioxidant, N-acetyl-L-cysteine, also efficiently decreased the intracellular ROS level in WC 256 cells, but did not affect the migration of the investigated cells. These results demonstrate that intact, unmodified ascorbic acid applied in physiologically relevant and non-toxic concentrations exerts an inhibitory effect on the migration of WC 256 carcinosarcoma cells, and that this may be one of the factors responsible for the anti-metastatic activity of vitamin C. However, our data does not support the hypothesis that the scavenging of intracellular ROS is the main mechanism in the inhibition of cancer cell migration by ascorbic acid.
Cell Mol Biol Lett 2008
PMID:Ascorbic acid inhibits the migration of Walker 256 carcinosarcoma cells. 1796 72

This study aimed to 1) assess whether substance P (SP) acts via neurokinin (NK)-1 and NK-2 receptors to stimulate neurogenic inflammation (indicated by formation of ICAM-1 expression and oxidative stress) following oil smoke exposure (OSE) in rats; and 2) determine if pretreatment with antioxidants ameliorates the deleterious effects of OSE. Rats were pretreated with NK-1 receptor antagonist CP-96345, NK-2 receptor antagonist SR-48968, vitamin C, or catechins. OSE was for 30-120 min. Rats were killed 0-8 h later. Total lung resistance (RL), airway smooth muscle activity (ASMA), lung ICAM-1 expression, neurogenic plasma extravasation (via India ink and Evans blue dye), bronchoalveolar lavage fluid SP concentrations, and reactive oxygen species formation [via lucigenin- and luminal-amplified chemiluminescence (CL)] were assessed. Lung histology was performed. SP concentrations increased significantly in nonpretreated rats following OSE in a dose-dependent manner. RL and total ASMA increased over time after OSE. Vitamin C and catechin pretreatments were associated with significantly reduced lucigenin CL 2 and 4 h after OSE. Pretreatment with catechins significantly reduced luminal CL counts 4 and 8 h after OSE. Evans blue levels were significantly reduced following 60 and 120 min of OSE in catechin- and CP-96345-pretreated rats. ICAM-1 protein expression was significantly decreased in all pretreatment groups after OSE. Thickening of the alveolar capillary membrane, focal hemorrhaging, interstitial pneumonitis, and peribronchiolar inflammation were apparent in OSE lungs. These findings suggest that SP acts via the NK-1 receptor to provoke neurogenic inflammation, oxidative stress, and ICAM-1 expression after OSE in rats.
Am J Physiol Lung Cell Mol Physiol 2008 May
PMID:Substance P acts via the neurokinin receptor 1 to elicit bronchoconstriction, oxidative stress, and upregulated ICAM-1 expression after oil smoke exposure. 1832 23

The effect of supplementation of ascorbic acid through enriched zooplankton [10%, 20% and 30% ascorbyl palmitate (AP) inclusion in diet of zooplankton] on different digestive enzyme activities during ontogeny of Labeo rohita larvae was studied from 4 day to 15 day post hatch. Ascorbic acid (AA) content in different groups of unenriched (8.6+/-0.71) and enriched zooplankton were, 750+/-29.3, 1409.1+/-45.5, 2009.21+/-199.2 mug/g respectively on dry matter basis with differences (P<0.05) between the treatments. A difference (P<0.05) was found in tissue AA level in different dietary groups. Low amylase, protease, lipase and alkaline phosphatase activities were present in rohu larvae from the mouth opening stage which showed increasing trend with the age of larvae and increasing dietary AA content. A clear dose-dependent modulation of digestive enzyme activities in response to 10%, 20% and 30% AP enriched zooplankton feeding was evidenced from positive correlations between dietary AA content with magnitude of elevation of enzyme activity in different groups. There were 57, 55, 29.2 and 2 fold increases in amylase activity; 7.35, 7.02, 4.43 and 2.73 fold increases in protease activity; 45.636, 41.50, 19.83 and 13.69 fold increases in lipase activity and 6, 5, 3, and 2 fold increases in alkaline phosphatase activity observed in the 15th day post hatch larvae fed 20%, 30%, 10%AP enriched and normal zooplankton respectively, than 4-day post hatch larvae of the respective groups. Enzyme activities were also positively correlated with specific growth rates of wet weight of rohu larvae at the 15th day post hatch. Increased AA might have played an important role in advancing morphological transformation of the digestive tract, protecting gastric mucosa and accelerating growth by the process of tissue formation, which necessitated the requirement of more nutrient thereby, increasing digestive enzyme activity. The regulatory role of AA in the modulation of different digestive enzymes activity and its physiological consequences of nutrient digestibility and utilization during ontogenesis could be extrapolated for better nutrient management of the larvae.
Comp Biochem Physiol A Mol Integr Physiol 2008 Apr
PMID:Modulation of digestive enzyme activities during ontogeny of Labeo rohita larvae fed ascorbic acid enriched zooplankton. 1832 33

We have earlier reported that the redox-active antioxidant, vitamin C (ascorbic acid), activates the lipid signaling enzyme, phospholipase D (PLD), at pharmacological doses (mM) in the bovine lung microvascular endothelial cells (BLMVECs). However, the activation of phospholipase A(2) (PLA(2)), another signaling phospholipase, and the modulation of PLD activation by PLA(2) in the ECs treated with vitamin C at pharmacological doses have not been reported to date. Therefore, this study aimed at the regulation of PLD activation by PLA(2) in the cultured BLMVECs exposed to vitamin C at pharmacological concentrations. The results revealed that vitamin C (3-10 mM) significantly activated PLA(2) starting at 30 min; however, the activation of PLD resulted only at 120 min of treatment of cells under identical conditions. Further studies were conducted utilizing specific pharmacological agents to understand the mechanism(s) of activation of PLA(2) and PLD in BLMVECs treated with vitamin C (5 mM) for 120 min. Antioxidants, calcium chelators, iron chelators, and PLA(2) inhibitors offered attenuation of the vitamin C-induced activation of both PLA(2) and PLD in the cells. Vitamin C was also observed to significantly induce the formation and release of the cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic acid (AA) metabolites and to activate the AA LOX in BLMVECs. The inhibitors of PLA(2), COX, and LOX were observed to effectively and significantly attenuate the vitamin C-induced PLD activation in BLMVECs. For the first time, the results of the present study revealed that the vitamin C-induced activation of PLD in vascular ECs was regulated by the upstream activation of PLA(2), COX, and LOX through the formation of AA metabolites involving oxidative stress, calcium, and iron.
Mol Cell Biochem 2008 Aug
PMID:Redox-active antioxidant modulation of lipid signaling in vascular endothelial cells: vitamin C induces activation of phospholipase D through phospholipase A2, lipoxygenase, and cyclooxygenase. 1849 33

This study was undertaken with the aim of developing an easy and quick means of analyzing the effect of various compounds on the synthesis and secretion of human type I collagen at the protein level. A modification of the ELISA method was used on HFF-1 cells. For the proof of concept, we used thirteen compounds most of which are known to be antioxidants. Each compound was tested at concentrations of 0, 10 and 100 microM on HFF-1 cells for 24 h. Thirteen sets of experiments for each compound were performed in ANOVA with three replicates. Duncan multiple range test (DMRT) was used to compare the mean values obtained from the treatment groups. From the results it was concluded that Vitamin C, undecylenic acid, conjugated linoleic acid, glycolic acid, and citric acid at 100 microM concentration could be used for anti-wrinkling or protection from premature aging, which requires enhancement of collagen synthesis. Lactic acid, EGCG, resveratrol, and retinol that can inhibit collagen synthesis effectively in a dose-dependent manner may be used for anti-fibrosis treatment purposes.
Mol Cells 2008 Dec 31
PMID:A rapid and sensitive screening system for human type I collagen with the aim of discovering potent anti-aging or anti-fibrotic compounds. 1881 Feb 49

We previously reported that tumor cells expressing p53 increase intracellular levels of reactive oxygen species (ROS). In this study, we described an inhibitory effect of vitamin C on replicative senescence. Vitamin C was found to inhibit p53-induced senescence in human bladder cancer EJ cells. The senescence-like phenotype (SLP) induced by p53, which showed a morphological change and an irreversible cell cycle arrest, was not observed in vitamin C-treated EJ cells. In addition, vitamin C did not significantly affect normal cell proliferation. We investigated the molecular mechanisms of the inhibitory effect of vitamin C on the development of replicative senescence in EJ cells. We found that vitamin C inhibited this p53-induced ROS generation. Moreover, p38 kinase which was activated during p53-induced senescence was not observed in vitamin C-treated EJ cells. SB203580, a chemical inhibitor of p38 kinase, was found to consistently inhibit p53-induced senescence. Therefore, it is suggested that vitamin C inhibits p53-induced senescence by preventing ROS generation, which in turn leads to the activation of p38 MAPKinase. These results reveal the inhibitory mechanism of vitamin C on cellular senescence.
Int J Mol Med 2008 Nov
PMID:Vitamin C inhibits p53-induced replicative senescence through suppression of ROS production and p38 MAPK activity. 1894 86


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