3 research outputs found

    Chronic alcohol consumption has greater impact on hepatic DNA hydroxymethylation in young mice relative to old

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    Aging and chronic alcohol consumption affects DNA methylation, changing gene transcription. It is not yet known whether these factors also alter DNA hydroxymethylation (hmC), an epigenetic mark produced by oxidation of methylcytosine.This is the first study demonstrating the effects of chronic alcohol consumption and aging on DNA hmC levels. Chronic alcohol consumption differently affects DNA hmC in young and old mice

    Aging alters global hepatic DNA hydroxymethylation in mice, as determined by a novel LC/MS-MS method

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    Aging is associated with changes in global DNA methylation (mC), but changes in DNA hydroxymethylation (hmC) are not established due to a relative lack of methods available to measure hmC. Both modifications can affect gene expression and may be important in aging. We have developed a method to measure 5'-methyl-2'-deoxycytidine and 5'-hydroxymethyl-2'-deoxycytidine in DNA using liquid chromatography/tandem mass spectrometry (LC/MS-MS) and used this method to assess global hmC and mC levels in hepatic tissue from young (9 months; n=10) and old (23 months; n=6) C57BL/6 male mice. DNA was enzymatically hydrolyzed and isotopomers [15N3]-2'-deoxycytidine and (methyl-d3, ring-6-d1)-5-methyl-2'-deoxycytidine were added as internal standards. The mixture of DNA hydrolysates and internal standards were separated through LC, and nucleosides of interest were detected by MS-MS in positive ion mode using multiple reaction monitoring. Global mC and hmC levels were calculated as a percentage of total deoxycytidine residues in genomic DNA. Liver tissue from old mice had significantly higher global hmC relative to young mice (0.32±0.02% vs 0.24±0.01%; p=0.02), while mC levels did not change. Using this new method we have found that aging is associated with an increase in global DNA hmC, a finding that may be useful in understanding the physiological mechanisms behind aging

    The chemical and biological activities of quinones: Overview and implications in analytical detection

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    Quinones are a class of natural and synthetic compounds that have several beneficial effects. Quinones are electron carriers playing a role in photosynthesis. As vitamins, they represent a class of molecules preventing and treating several illnesses such as osteoporosis and cardiovascular diseases. Quinones, by their antioxidant activity, improve general health conditions. Many of the drugs clinically approved or still in clinical trials against cancer are quinone related compounds. Quinones have also toxicological effects through their presence as photoproducts from air pollutants. Quinones are fast redox cycling molecules and have the potential to bind to thiol, amine and hydroxyl groups. The aforementioned properties make the analytical detection of quinones problematic. However, recent advances of the available analytical techniques along with the possibility of using labeled compound facilitate their detection hence allowing a better understanding of their action. This review summarizes the current knowledge with respect to the oxido-reductive and electrophilic properties of quinones as well as to the analytical tools used for their analysis. It includes a general introduction about the physiological, and therapeutical functions of quinones. A number of studies are reported to cover the chemical reactivity in an attempt to understand quinones as biologically active compounds. Data ranging from normal analytical methods to study quinones derived from plant or biological matrices to the use of labeled compounds are presented. 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