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The inhibition of the mammalian DNA methyltransferase 3a (Dnmt3a) by dietary black tea and coffee polyphenols.

Rajavelu A, Tulyasheva Z, Jaiswal R, Jeltsch A, Kuhnert N - BMC Biochem. (2011)

Bottom Line: Previously, the inhibition of DNA methyltransferase 1 was shown by dietary polyphenols and epi-gallocatechin gallate (EGCG), the main polyphenolic constituent of green tea, and 5-caffeoyl quinic acid, the main phenolic constituent of the green coffee bean.For theaflavin 3,3 digallate and thearubigins IC50 values in the lower micro molar range were observed, which when compared to pharmacokinetic data available, suggest an effect of physiological relevance.Since Dnnmt3a has been associated with development, cancer and brain function, these data suggest a biochemical mechanism for the beneficial health effect of black tea and coffee and a possible molecular mechanism for the improvement of brain performance and mental health by dietary polyphenols.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chemistry, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.

ABSTRACT

Background: Black tea is, second only to water, the most consumed beverage globally. Previously, the inhibition of DNA methyltransferase 1 was shown by dietary polyphenols and epi-gallocatechin gallate (EGCG), the main polyphenolic constituent of green tea, and 5-caffeoyl quinic acid, the main phenolic constituent of the green coffee bean.

Results: We studied the inhibition of DNA methyltransferase 3a by a series of dietary polyphenols from black tea such as theaflavins and thearubigins and chlorogenic acid derivatives from coffee. For theaflavin 3,3 digallate and thearubigins IC50 values in the lower micro molar range were observed, which when compared to pharmacokinetic data available, suggest an effect of physiological relevance.

Conclusions: Since Dnnmt3a has been associated with development, cancer and brain function, these data suggest a biochemical mechanism for the beneficial health effect of black tea and coffee and a possible molecular mechanism for the improvement of brain performance and mental health by dietary polyphenols.

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Methyltransferase activity of the purified Dnmt3a-C. Example of the methylation kinetics carried out with purified Dnmt3a-C. Initial slopes were determined by linear regression analysis of the initial linear parts of the reaction progress curves.
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Figure 3: Methyltransferase activity of the purified Dnmt3a-C. Example of the methylation kinetics carried out with purified Dnmt3a-C. Initial slopes were determined by linear regression analysis of the initial linear parts of the reaction progress curves.

Mentions: The purified Dnmt3a-C was catalytically highly active (Figure 3). For an initial screening of the twenty four inhibitor candidates, Dnmt3a-C DNA methylation kinetics were carried out in the presence of 100 μM of compound. Rates of DNA methylation were derived by linear regression of the initial phase of the reaction progress curves. The reaction rates were compared with control reactions carried out after addition of a corresponding volume of DMSO to ensure identical reaction conditions, because DMSO had been shown before to influence the activity of Dnmt3a [41]. As shown in Figure 4, four of the compounds had a substantial inhibitory effect for the in vitro Dnmt3a-C activity (N6-N8 and N12). To determine IC50 values, DNA methylation kinetics were carried out in the presence of variable concentrations of the inhibitors, initial slopes derived and the activity profile analysed by fitting of the experimental data to the equation:


The inhibition of the mammalian DNA methyltransferase 3a (Dnmt3a) by dietary black tea and coffee polyphenols.

Rajavelu A, Tulyasheva Z, Jaiswal R, Jeltsch A, Kuhnert N - BMC Biochem. (2011)

Methyltransferase activity of the purified Dnmt3a-C. Example of the methylation kinetics carried out with purified Dnmt3a-C. Initial slopes were determined by linear regression analysis of the initial linear parts of the reaction progress curves.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3102611&req=5

Figure 3: Methyltransferase activity of the purified Dnmt3a-C. Example of the methylation kinetics carried out with purified Dnmt3a-C. Initial slopes were determined by linear regression analysis of the initial linear parts of the reaction progress curves.
Mentions: The purified Dnmt3a-C was catalytically highly active (Figure 3). For an initial screening of the twenty four inhibitor candidates, Dnmt3a-C DNA methylation kinetics were carried out in the presence of 100 μM of compound. Rates of DNA methylation were derived by linear regression of the initial phase of the reaction progress curves. The reaction rates were compared with control reactions carried out after addition of a corresponding volume of DMSO to ensure identical reaction conditions, because DMSO had been shown before to influence the activity of Dnmt3a [41]. As shown in Figure 4, four of the compounds had a substantial inhibitory effect for the in vitro Dnmt3a-C activity (N6-N8 and N12). To determine IC50 values, DNA methylation kinetics were carried out in the presence of variable concentrations of the inhibitors, initial slopes derived and the activity profile analysed by fitting of the experimental data to the equation:

Bottom Line: Previously, the inhibition of DNA methyltransferase 1 was shown by dietary polyphenols and epi-gallocatechin gallate (EGCG), the main polyphenolic constituent of green tea, and 5-caffeoyl quinic acid, the main phenolic constituent of the green coffee bean.For theaflavin 3,3 digallate and thearubigins IC50 values in the lower micro molar range were observed, which when compared to pharmacokinetic data available, suggest an effect of physiological relevance.Since Dnnmt3a has been associated with development, cancer and brain function, these data suggest a biochemical mechanism for the beneficial health effect of black tea and coffee and a possible molecular mechanism for the improvement of brain performance and mental health by dietary polyphenols.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chemistry, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.

ABSTRACT

Background: Black tea is, second only to water, the most consumed beverage globally. Previously, the inhibition of DNA methyltransferase 1 was shown by dietary polyphenols and epi-gallocatechin gallate (EGCG), the main polyphenolic constituent of green tea, and 5-caffeoyl quinic acid, the main phenolic constituent of the green coffee bean.

Results: We studied the inhibition of DNA methyltransferase 3a by a series of dietary polyphenols from black tea such as theaflavins and thearubigins and chlorogenic acid derivatives from coffee. For theaflavin 3,3 digallate and thearubigins IC50 values in the lower micro molar range were observed, which when compared to pharmacokinetic data available, suggest an effect of physiological relevance.

Conclusions: Since Dnnmt3a has been associated with development, cancer and brain function, these data suggest a biochemical mechanism for the beneficial health effect of black tea and coffee and a possible molecular mechanism for the improvement of brain performance and mental health by dietary polyphenols.

Show MeSH
Related in: MedlinePlus