Activation and induction of glycine N-methyltransferase by retinoids are tissue- and gender-specific

McMullen, Mary H.; Rowling, Matthew J.; Ozias, Marlies K.; Schalinske, Kevin L.

doi:10.1016/s0003-9861(02)00030-9

Cited by 35 publications

(46 citation statements)

References 44 publications

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“…Retinoid compounds have been shown to activate and induce hepatic GNMT in rats (Rowling and Schalinske, 2001), with activation being both liver-specific and more efficient in male than female rats (McMullen et al, 2002). In addition, retinoic acid and glucocorticoid treatment are independently capable of inducing GNMT, and the coadministration of all-trans retinoic acid plus dexamethasone has an additive effect on GNMT induction (Rowling and Schalinske, 2003).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the 5′ regulatory region of the human Glycine N-methyltransferase gene

Lee¹,

Shih²,

Wu³

et al. 2009

Gene

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Section: Discussionmentioning

confidence: 99%

Characterization of the 5′ regulatory region of the human Glycine N-methyltransferase gene

Lee¹,

Shih²,

Wu³

et al. 2009

Gene

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“…All-trans-retinoic acid (RA) has been shown to induce hepatic GNMT activity and protein abundance, resulting in the loss of methyl groups for subsequent transmethylation reactions (13)(14)(15)(16). Moreover, dexamethasone (DEX) was just as effective as RA in the induction of GNMT activity in rat liver and hepatoma cells, and the co-administration of both DEX and RA induced GNMT in an additive fashion (17).…”

mentioning

confidence: 99%

Modulation of Methyl Group Metabolism by Streptozotocin-induced Diabetes and All-trans-retinoic Acid

Nieman

Rowling

Garrow

et al. 2004

Journal of Biological Chemistry

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The hepatic enzyme glycine N-methyltransferase (GNMT) plays a major role in the control of methyl group and homocysteine metabolism. Because disruption of these vital pathways is associated with numerous pathologies, understanding GNMT control is important for evaluating methyl group regulation. Recently, gluconeogenic conditions have been shown to modulate homocysteine metabolism and treatment with glucocorticoids and/or all-trans-retinoic acid (RA)-induced active GNMT protein, thereby leading to methyl group loss. This study was conducted to determine the effect of diabetes, alone and in combination with RA, on GNMT regulation. Diabetes and RA increased GNMT activity 87 and 148%, respectively. Moreover, the induction of GNMT activity by diabetes and RA was reflected in its abundance. Cell culture studies demonstrated that pretreatment with insulin prevented GNMT induction by both RA and dexamethasone. There was a significant decline in homocysteine concentrations in diabetic rats, owing in part to a 38% increase in the abundance of the transsulfuration enzyme cystathionine ␤-synthase; treatment of diabetic rats with RA prevented cystathionine ␤-synthase induction. A diabetic state also increased the activity of the folate-independent homocysteine remethylation enzyme betaine-homocysteine S-methyltransferase, whereas the activity of the folatedependent enzyme methionine synthase was diminished 52%. In contrast, RA treatment attenuated the streptozotocin-mediated increase in betaine-homocysteine Smethyltransferase, whereas methionine synthase activity remained diminished. These results indicate that both a diabetic condition and RA treatment have marked effects on the metabolism of methyl groups and homocysteine, a finding that may have significant implications for diabetics and their potential sensitivity to retinoids.

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“…To date, there have been no reports testing the hypothesis that activation of GNMT in cells in culture result in reduced DNA methylation; however, a few reports have described dietary manipulation of GNMT in rodents. [150][151][152] For example, diets supplemented with vitamin A and its derivatives (e.g., all-trans retinoic acid, ATRA) result in increased GNMT activity and hypomethylated DNA in rat hepatocytes, while decreases in dietary folate, choline, betaine, and vitamins B6 and B12 also result in decreased DNA methylation in specific tissues. Thus, alterations in the availability of single-carbon metabolism components (e.g., methyl donors) and adjusting the nutrient availability of methyl donors represent possible in vitro approaches to demethylate DNA and restore cell differentiation potential.…”

Section: B Limiting the Methyl Group Supplymentioning

confidence: 99%

The Epigenetics of Adult (Somatic) Stem Cells

Eilertsen

Floyd

Gimble

2008

Crit Rev Eukar Gene Expr

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While genetic studies have provided a wealth of information about health and disease, there is a growing awareness that individual characteristics are also determined by factors other than genetic sequences. These "epigenetic" changes broadly encompass the influence of the environment on gene regulation and expression and in a more narrow sense, describe the mechanisms controlling DNA methylation, histone modification and genetic imprinting. In this review, we focus on the epigenetic mechanisms that regulate adult (somatic) stem cell differentiation, beginning with the metabolic pathways and factors regulating chromatin structure and DNA methylation and the molecular biological tools that are currently available to study these processes. The role of these epigenetic mechanisms in manipulating adult stem cells is followed by a discussion of the challenges and opportunities facing this emerging field.

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Activation and induction of glycine N-methyltransferase by retinoids are tissue- and gender-specific

Cited by 35 publications

References 44 publications

Characterization of the 5′ regulatory region of the human Glycine N-methyltransferase gene

Characterization of the 5′ regulatory region of the human Glycine N-methyltransferase gene

Modulation of Methyl Group Metabolism by Streptozotocin-induced Diabetes and All-trans-retinoic Acid

The Epigenetics of Adult (Somatic) Stem Cells

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