Novel aspects of vitamin C: how important is glypican-1 recycling?

Fransson, Lars‐Âke; Mani, Katrin

doi:10.1016/j.molmed.2007.02.005

Cited by 29 publications

(20 citation statements)

References 56 publications

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“…5) It is well known that AsA is an important cofactor required both in catecholamine biosynthesis and in adrenal steroidogenesis, and that it functions as a water-soluble antioxidant in the adrenal gland. [5][6][7][8][9] The cellular uptake of AsA and its distribution in cells are important factors that determine its inherent activity. Studies of tissue distribution of radioactivity in animals after injection of 14 C-labeled AsA ( 14 C-AsA) were reported in the 1960s, showing a remarkable uptake of radioactivity in the adrenal glands, pituitary glands and parotid glands.…”

mentioning

confidence: 99%

6-Deoxy-6-[131I]iodo-L-ascorbic Acid for the in Vivo Study of Ascorbate: Autoradiography, Biodistribution in Normal and Hypolipidemic Rats, and in Tumor-Bearing Nude Mice

Kim

Yamamoto

Gondo

et al. 2009

Biological & Pharmaceutical Bulletin

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Over the past few decades, a number of radiopharmaceuticals for noninvasive imaging of the adrenal glands by the nuclear imaging technique have been evolved, designed by targeting specific metabolic or synthetic processes within the gland.1,2) Among the current developments and the expansion of new molecular imaging modalities and specific probes, adrenal scintigraphy using more specific radiotracers to obtain functional information for tissue characterization is still challenging. 3,4)The adrenal gland is among the organs with the highest concentration of L-ascorbic acid (AsA) in the body and is particularly sensitive to deficiencies of AsA.5) It is well known that AsA is an important cofactor required both in catecholamine biosynthesis and in adrenal steroidogenesis, and that it functions as a water-soluble antioxidant in the adrenal gland. [5][6][7][8][9] The cellular uptake of AsA and its distribution in cells are important factors that determine its inherent activity. Studies of tissue distribution of radioactivity in animals after injection of 14 C-labeled AsA ( 14 C-AsA) were reported in the 1960s, showing a remarkable uptake of radioactivity in the adrenal glands, pituitary glands and parotid glands.10-12) Diagnostic application of AsA as a radiotracer for imaging the adrenals, however, remains to be limited by relatively high accumulations of 14 C-AsA in the liver and kidneys. 13)Recent biochemical studies have demonstrated that AsA is taken up into cells by the sodium-dependent vitamin C transporter (SVCT-1 and -2), whereas oxidized vitamin C (dehydroascorbic acid) is transported via glucose transporters. [14][15][16][17][18][19] SVCT-1 is expressed in epithelial organs such as the liver and kidneys, whereas SVCT-2 is found in the adrenal glands and lungs. [14][15][16][17][18][19] In particular, SVCT-2 is primarily responsible for the uptake of AsA from blood circulation into the adrenal cells. [14][15][16][17][18][19] The adrenals have been shown to have the largest falls in the AsA levels in mice with a deficiency of 20) and the influence of the depletion of tissue AsA on tissue catecholamines was found to be most prominent in the adrenals. 21,22) In addition, it has recently been shown that overexpression of adrenal SVCT-2 mRNA in diabetic mice resulted in increased uptake of AsA. 23) Thus, it is most likely that the AsA transport mechanism plays an important role in the pathologic processes of the adrenals. 24) We became interested in the possibility that appropriate structural AsA analogs with specific transport characteristics, if possessing favorable in vivo distribution properties, might be used as tracer agents for the visualization of biochemical events associated with the action of AsA in the adrenal glands. Several AsA analogs labeled with 18 F, 131 I, 125 I, or 99m Tc were prepared and their potential imaging characteristics were evaluated in animals. [25][26][27][28][29][30][31] 6-Deoxy-6-iodo-L-ascorbic acid (6-IAsA) has been shown to be an effective inhibitor of AsA transport, with tran...

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confidence: 99%

6-Deoxy-6-[131I]iodo-L-ascorbic Acid for the in Vivo Study of Ascorbate: Autoradiography, Biodistribution in Normal and Hypolipidemic Rats, and in Tumor-Bearing Nude Mice

Kim

Yamamoto

Gondo

et al. 2009

Biological & Pharmaceutical Bulletin

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“…Similarly, extracellular DHA is rapidly excreted or immediately hydrolyzed. Hence, only a protective, reduced form of VC is detected in plasma and intracellularly [27,31].…”

Section: Cellular Transport Of Vitamin Cmentioning

confidence: 99%

“…Sodium-dependent VC transporter 1 is responsible mainly for intestinal absorption and renal reabsorption. Sodium-dependent VC transporter 1 carries VC across the intestinal barrier, while further VC transport from blood into the cells depends on SVTC2 transporters [26][27][28].…”

Section: Cellular Transport Of Vitamin Cmentioning

confidence: 99%

“…Sodium-dependent VC transporter 2 has been implicated in the maintenance of intracellular VC levels vital for the neuronal functions and protection against oxidative stress. Sodium-dependent VC transporter 2 has a higher affinity for AA, therefore it protects metabolically active cells (neurons, chondrocytes, keratinocytes) against oxidative stress [25][26][27]29].…”

Section: Cellular Transport Of Vitamin Cmentioning

confidence: 99%

“…Gradient-driven transport of the oxidized, hexose-like dehydroascorbic acid is mediated by low-affinity, highcapacity sodium-independent glucose transporters particularly GLUT1, GLUT3 and GLUT4, with no affinity for AA and ascorbate [17,25,27]. In human erythrocytes the association of GLUT1 C-terminal peptide with stomatin, an integral erythrocyte membrane protein is responsible for the preferential uptake of DHA.…”

Section: Cellular Transport Of Vitamin Cmentioning

confidence: 99%

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Vitamin C: is it time to re-evaluate its role in health and disease?

Rutkowski¹,

Rutkowski²,

Rutkowska-Talipska³

et al. 2012

pdia

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A b s t r a c tVitamin C (VC; ascorbic acid, AA) is synthesised from glucose in the liver of most mammals, but not in humans. Synthetic AA supplementation is often necessary to prevent vitamin C deficiency. Intracellularly AA is reversibly oxidized to an ascorbic radical which converts into dehydroascorbic acid (DHA). Ascorbic acid crosses cell membranes with SVCT1, SVCT2 or GLUT1, GLUT3 and GLUT4 transporters. Recommended daily allowance for VC is around 75 mg/day for women and 90 mg/day for men. This seems to be too low in relation to real human body needs and does not ensure true health protection. There are ongoing studies re-evaluating the role of VC in cancer treatment. Therefore, it would be also appropriate to reassess its use as a specific drug in the prevention and therapy of asthma, allergic rhinitis and atopic dermatitis. K Ke ey y w wo or rd ds s: : vitamin C, deficiency, absorption, recommended dietary allowance, therapy.

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