Hydroquinone Increases 5-Hydroxymethylcytosine Formation through Ten Eleven Translocation 1 (TET1) 5-Methylcytosine Dioxygenase

Coulter, Jonathan B.; O’Driscoll, Cliona; Bressler, Joseph

doi:10.1074/jbc.m113.491365

Cited by 86 publications

(75 citation statements)

References 35 publications

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“…Nevertheless, initial biochemical studies did not support this contention; reducing agents other than ascorbate were apparently insufficient to enhance TET activity in vitro [45,50,51,53]. Subsequent cell culture experiments using quinones as reducing agents [54,55], and further in vitro experiments at physiological pH [37] have now challenged this conclusion. Ascorbate has been found not to enhance TET activity when in the presence of sufficient Fe 2+ , demonstrating it is not an obligatory cofactor [37].…”

Section: Vitamin a Enhances Tet Expression Vitamin C Potentiates Tetmentioning

confidence: 92%

Modulating Epigenetic Memory through Vitamins and TET: Implications for Regenerative Medicine and Cancer Treatment

Hore

2017

Epigenomics

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Vitamins A and C represent unrelated sets of small molecules that are essential to the human diet and have recently been shown to intensify erasure of epigenetic memory in naive embryonic stem cells. These effects are driven by complementary enhancement of the ten-eleven translocation (TET) demethylases -vitamin A stimulates TET expression, whereas vitamin C potentiates TET catalytic activity. Vitamin A and C cosupplementation synergistically enhances reprogramming of differentiated cells to the naive state, but overuse may exaggerate instability of imprinted genes. As such, optimizing their use in culture media will be important for regenerative medicine and mammalian transgenics. In addition, mechanistic perception of how these vitamins interact with the epigenome may be relevant for understanding cancer and improving patient treatment. Figure 1A), and both are associated with a long recorded history. Nightblindness, an early symptom of vitamin A deficiency, and its cure through liver consumption, was known to Egyptians in the prehistoric period [1]. Equally, the debilitating effects of scurvy (vitamin C deficiency) among sailors, and its treatment with oranges, was registered as far back as 1498 [2]. Vitamins A and C also have a lengthy and rich history in scientific literature; in 1753 James Lind described the first controlled clinical trial where various antiscorbutic treatments were tested on British seamen and in 1929, Frederick Gowland Hopkins was co-awarded the Nobel Prize in Medicine for the 'discovery of vitamins' following milk supplementation experiments in vitamin A deficient mice [3]. Eventual isolation of the respective compounds underlying both vitamins led to Nobel Prizes in Chemistry and Medicine in 1937 [4]. Since this time, a considerable amount of scientific progress (and at times conjecture) has been associated with vitamins A and C, and their respective biological effects touch disciplines as divergent as development and dermatology.One of the most recently discovered fields that vitamins A and C impact upon is epigenetics [5][6][7]. New research has shown that both vitamins drive active removal of DNA methylation in embryonic stem cells (ESCs) by enhancing the same family of ten-eleven translocation (TET) enzymes, and in doing so, help erase DNA methylation and the epigenetic memory encoded by it to improve the reprogramming of differentiated cells to an embryonic-like state. Here I review the effects of vitamins A and C on DNA methylation and epigenetic memory in stem cells, and outline their significance for the fields For reprint orders, please contact: reprints@futuremedicine.com

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Section: Vitamin a Enhances Tet Expression Vitamin C Potentiates Tetmentioning

confidence: 92%

Modulating Epigenetic Memory through Vitamins and TET: Implications for Regenerative Medicine and Cancer Treatment

Hore

2017

Epigenomics

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“…On the other hand, several known confounders are capable of changing 5-hmC levels in the human body; for example, vitamin C and hydroquinone are both capable of increasing 5-hmC levels in vitro [27,28]. Lifestyle factors, such as food and medicine intake as well as cosmetics use, also cannot be excluded from factors that may influence the 5-hmC level in the human stomach.…”

Section: Discussionmentioning

confidence: 99%

Robust quantitative assessments of cytosine modifications and changes in the expressions of related enzymes in gastric cancer

Kurabe

Matsushima

et al. 2014

Gastric Cancer

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Background The rediscovery of 5-hydroxymethylcytosine, the ten-eleven translocation (TET) family, thymine-DNA glycosylase (TDG) and isocitrate dehydrogenase (IDH) have opened new avenues in the study of DNA demethylation pathways in gastric cancer (GC). We performed a comprehensive and robust analysis of these genes and modified cytosines in gastric cancer. Methods Liquid chromatography mass spectrometry/ mass spectrometry (LC-MS/MS) was used to assess 5-methyldeoxycytidine (5-mC), 5-hydroxymethyldeoxycytidine (5-hmC), 5-formyldeoxycytidine (5-fC) and 5-carboxyldeoxycytidine (5-caC) quantitatively in tumorous and non-tumorous regions of GCs; [D 2 ]-5-hmC was used as an internal standard. Expression levels of the genes TET1, TET2, TET3, TDG, IDH1 and IDH2 were measured using a real-time reverse transcription polymerase chain reaction (RT-PCR) and were compared to the clinical attributes of each case. Using HEK293T cells the effects of introducing plasmids containing full-length TET1, TET2, and TET3 and 7 variants of the TET2 catalytic domain were evaluated in terms of their effect on cytosine demethylation. Results LC-MS/MS showed that 5-hmC was significantly decreased in tumorous portions. 5-mC was also moderately decreased in tumors, while 5-fC and 5-caC were barely detectable. The expressions of TET1, TET2, TET3, TDG and IDH2, but not IDH1, were notably decreased in GCs, compared with the adjacent non-tumor portion. TET1 123Gastric Cancer (2015( ) 18:516-525 DOI 10.1007 expression and the 5-hmC levels determined using LC-MS/ MS had a significantly positive correlation and TET1 protein had a greater effect on the increase in 5-hmC than TET2 and TET3 in HEK293T cells. Conclusions The loss of 5-hmC and the down-regulation of TET1-3, TDG and IDH2 were found in GCs. The loss of 5-hmC in GCs was mainly correlated with the down-regulation of TET1.

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“…However several authors are now received new experimental proofs of free radical mechanism of DNA demethylation by the stage oxidative mechanism of methyl group of 5-methylcytosine ( Figure 2). As it can be seen in Figure 2, DNA demethylation is carried out by a free radical mechanism catalyzed by the iron-dependent enzymes ten-eleven translocations (TET [105]. Similarly, redox-active quinones, the other superoxide producers activated oxidative conversion of 5mC to 5hmC by the TET dioxygenase-catalyzed reaction [106].…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Superoxide Signaling in Epigenetic Processes: Relation to Aging and Cancer

Afanas’ev¹

2015

Aging and disease

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Superoxide is a precursor of many free radicals and reactive oxygen species (ROS) in biological systems. It has been shown that superoxide regulates major epigenetic processes of DNA methylation, histone methylation, and histone acetylation. We suggested that superoxide, being a radical anion and a strong nucleophile, could participate in DNA methylation and histone methylation and acetylation through mechanism of nucleophilic substitution and free radical abstraction. In nucleophilic reactions superoxide is able to neutralize positive charges of methyl donors S-adenosyl-L-methionine (SAM) and acetyl-coenzyme A (AcCoA) enhancing their nucleophilic capacity or to deprotonate cytosine. In the reversed free radical reactions of demethylation and deacetylation superoxide is formed catalytically by the (Tet) family of dioxygenates and converted into the iron form of hydroxyl radical with subsequent oxidation and final eradication of methyl substituents. Double role of superoxide in these epigenetic processes might be of importance for understanding of ROS effects under physiological and pathological conditions including cancer and aging.

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Hydroquinone Increases 5-Hydroxymethylcytosine Formation through Ten Eleven Translocation 1 (TET1) 5-Methylcytosine Dioxygenase

Cited by 86 publications

References 35 publications

Modulating Epigenetic Memory through Vitamins and TET: Implications for Regenerative Medicine and Cancer Treatment

Modulating Epigenetic Memory through Vitamins and TET: Implications for Regenerative Medicine and Cancer Treatment

Robust quantitative assessments of cytosine modifications and changes in the expressions of related enzymes in gastric cancer

Mechanisms of Superoxide Signaling in Epigenetic Processes: Relation to Aging and Cancer

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