Recycling of vitamin C from its oxidized forms by human endothelial cells

May, James M.; Qu, Zhi-chao; Neel, Dustin; Li, Xia

doi:10.1016/s0167-4889(03)00043-0

Cited by 52 publications

(35 citation statements)

References 38 publications

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“…S3). These results are concordant with the literature regarding the bioconversion and uptake of DHA, reflected in the relative steady-state concentrations of DHA and Vitamin C in cells (35).…”

Section: Time-resolved Magnetic Resonance Spectroscopy Confirms Rapidsupporting

confidence: 92%

Hyperpolarized ¹³ C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

Keshari

Kurhanewicz

Bok

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

152

159

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Reduction and oxidation (redox) chemistry is involved in both normal and abnormal cellular function, in processes as diverse as circadian rhythms and neurotransmission. Intracellular redox is maintained by coupled reactions involving NADPH, glutathione (GSH), and vitamin C, as well as their corresponding oxidized counterparts. In addition to functioning as enzyme cofactors, these reducing agents have a critical role in dealing with reactive oxygen species (ROS), the toxic products of oxidative metabolism seen as culprits in aging, neurodegenerative disease, and ischemia/ reperfusion injury. Despite this strong relationship between redox and human disease, methods to interrogate a redox pair in vivo are limited. Here we report the development of [1-13 C] dehydroascorbate [DHA], the oxidized form of Vitamin C, as an endogenous redox sensor for in vivo imaging using hyperpolarized 13 C spectroscopy. In murine models, hyperpolarized [1-13 C] DHA was rapidly converted to [1-13 C] vitamin C within the liver, kidneys, and brain, as well as within tumor in a transgenic prostate cancer mouse. This result is consistent with what has been previously described for the DHA/Vitamin C redox pair, and points to a role for hyperpolarized [1-13 C] DHA in characterizing the concentrations of key intracellular reducing agents, including GSH. More broadly, these findings suggest a prognostic role for this new redox sensor in determining vulnerability of both normal and abnormal tissues to ROS.MRI | molecular imaging | probe | kinetics

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Section: Time-resolved Magnetic Resonance Spectroscopy Confirms Rapidsupporting

confidence: 92%

Hyperpolarized ¹³ C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

Keshari

Kurhanewicz

Bok

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

152

159

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“…GLUT1 and GLUT3 transfer just the DHA form of Vitamin C [23]. When DHA entersit is cells rapidly reduced to ascorbate [24]. In the body, it appears that SVCTs are the predominant system for vitamin C transport.…”

Section: Absorption and Transportmentioning

confidence: 99%

An Overview of the Characteristics and Function of Vitamin C in Various Tissues: Relying on its Antioxidant Function

Akbari

Jelodar

Nazifi

et al. 2016

Zahedan J Res Med Sci

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Vitamin C (L-ascorbic acid or ascorbate) is a biomolecule that participates in many biochemical processes. It is an essential nutrient for humans, however, in some species such as rodents and guinea pigs is synthesized. It has a variety of functions in the body that we might venture to say make it a very important antioxidant nature and pro-oxidant. L-ascorbic acidic a reduced form of vitamin C and dehydroascorbic acid (DHA) is the oxidized form of ascorbate, both L-ascorbic acid and dihydroascorbic acid retain the vitamin C activity. Dehydro-ascorbate is reconverted to ascorbate in the cytosol by cytochrome b reductase and thioredoxin reductase in reactions involving NADH and NADPH, respectively. Ascorbate is transported into the cell via the sodium-dependent vitamin C transporters (SVCTs), which causes accumulation of ascorbate within cells against a concentration gradient. Dehydroascorbic acid, the oxidized form of ascorbate, is transported via glucose transporters family (GLUTs). The highest concentrations of ascorbate in the body are found in brain and adrenal gland. Vitamin C also acts as a co-factor in several enzyme reactions. This vitamin is an essential biochemical factor in the reproductive process. The pharmacophore of vitamin C is the ascorbate, ascorbate is an antioxidant.Ascorbate is a neuromodulator of glutamatergic and dopaminergic system and related behaviors. It also improves components of the immune system. Given the wide role of ascorbate, further investigation is necessary to evaluate the exact mechanism(s) underlying these effects. In this review we will consider a short overview of the characteristics and function of vitamin C (relying on antioxidant function) in various tissues.

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“…2). For example, endothelial cells and macrophages possess both GSH and NADPH-dependent mechanisms for recycling ascorbate (May et al, 2001;May et al, 2003a), although GSHdependent ascorbate recycling was not observed in HL-60 leukemic cells (Guaiquil et al, 1997), or human skin keratinocytes (Savini et al, 2000). GSH and other cellular thiols can also directly reduce DHA to ascorbate (Winkler et al, 1994), although this process is not as efficient as enzyme-mediated reduction.…”

Section: Ascorbate Recycling In Vascular Cellsmentioning

confidence: 99%

Inflammation in the vascular bed: Importance of vitamin C

Aguirre

May

2008

Pharmacology & Therapeutics

Self Cite

110

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Despite decreases in atherosclerotic coronary vascular disease over the last several decades, atherosclerosis remains a major cause of mortality in developed nations. One possible contributor to this residual risk is oxidant stress, which is generated by the inflammatory response of atherosclerosis. Although there is a wealth of in vitro, cellular, and animal data supporting a protective role for antioxidant vitamins and nutrients in the atherosclerotic process, the best clinical trials have been negative. This may be due to the fact that antioxidant therapies are applied "too little and too late." This review considers the role of vitamin C, or ascorbic acid in preventing the earliest inflammatory changes in atherosclerosis. It focuses on the three major vascular cell types involved in atherosclerosis: endothelial cells, vascular smooth muscle cells, and macrophages. Ascorbate chemistry, recycling, and function are described for these cell types, with emphasis on whether and how the vitamin might affect the inflammatory process. For endothelial cells, ascorbate helps to prevent endothelial dysfunction, stimulates type IV collagen synthesis, and enhances cell proliferation. For vascular smooth muscle cells, ascorbate inhibits dedifferentiation, recruitment, and proliferation in areas of vascular damage. For macrophages, ascorbate decreases oxidant stress related to their activation, decreases uptake and degradation of oxidized LDL in some studies, and enhances several aspects of their function. Although further studies of ascorbate function in these cell types and in novel animal models are needed, available evidence generally supports a salutary role for this vitamin in ameliorating the earliest stages of atherosclerosis.

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Recycling of vitamin C from its oxidized forms by human endothelial cells

Cited by 52 publications

References 38 publications

Hyperpolarized ¹³ C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

Hyperpolarized ¹³ C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

An Overview of the Characteristics and Function of Vitamin C in Various Tissues: Relying on its Antioxidant Function

Inflammation in the vascular bed: Importance of vitamin C

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Recycling of vitamin C from its oxidized forms by human endothelial cells

Cited by 52 publications

References 38 publications

Hyperpolarized 13 C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

Hyperpolarized 13 C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

An Overview of the Characteristics and Function of Vitamin C in Various Tissues: Relying on its Antioxidant Function

Inflammation in the vascular bed: Importance of vitamin C

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Resources

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Hyperpolarized ¹³ C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging

Hyperpolarized ¹³ C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging