Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression

(S)-Adenosylmethionine (SAM) is a critical element of melatonin synthesis as the methyl donor in the last step of the pathway, the O-methylation of N-acetyl 5-hydroxytryptamine by hydroxyindole-O-methyltransferase. The activity of the enzyme that synthesizes SAM, methionine adenosyltransferase (MAT)...

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Main Authors: Jong So Kim, Steven L. Coon, Seth Blackshaw, Constance L. Cepko, Morten Møller, Sujira Mukda, Wan Qian Zhao, Clivel G. Charlton, David C. Klein
Other Authors: National Institute of Child Health and Human Development
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Published: 2018
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/16385
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spelling th-mahidol.163852018-06-21T15:10:20Z Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression Jong So Kim Steven L. Coon Seth Blackshaw Constance L. Cepko Morten Møller Sujira Mukda Wan Qian Zhao Clivel G. Charlton David C. Klein National Institute of Child Health and Human Development Harvard Medical School Panum Institute Mahidol University Meharry Medical College Johns Hopkins University Life Sciences Research Foundation National Institutes of Health, Bethesda Biochemistry, Genetics and Molecular Biology (S)-Adenosylmethionine (SAM) is a critical element of melatonin synthesis as the methyl donor in the last step of the pathway, the O-methylation of N-acetyl 5-hydroxytryptamine by hydroxyindole-O-methyltransferase. The activity of the enzyme that synthesizes SAM, methionine adenosyltransferase (MAT), increases 2.5-fold at night in the pineal gland. In this study, we found that pineal MAT2A mRNA and the protein it encodes, MAT II, also increase at night, suggesting that the increase in MAT activity is caused by an increase in MAT II gene products. The night levels of MAT2A mRNA in the pineal gland were severalfold higher than in other neural and non-neural tissues examined, consistent with the requirement for SAM in melatonin synthesis. Related studies indicate that the nocturnal increase in MAT2A mRNA is caused by activation of a well described neural pathway that mediates photoneural-circadian regulation of the pineal gland. MAT2A mRNA and MAT II protein were increased in organ culture by treatment with norepinephrine (NE), the sympathetic neurotransmitter that stimulates the pineal gland at night. NE is known to markedly elevate pineal cAMP, and here it was found that cAMP agonists elevate MAT2A mRNA levels by increasing MAT2A mRNA synthesis and that drugs that block cAMP activation of cAMP dependent protein kinase block effects of NE. Therefore, the NE-cAMP dependent increase in pineal MAT activity seems to reflect an increase in MAT II protein, which occurs in response to cAMP→protein kinase-dependent increased MAT2A expression. The existence of this MAT regulatory system underscores the importance that MAT plays in melatonin biogenesis. These studies also point to the possibility that SAM production in other tissues might be regulated through cAMP. 2018-06-21T08:10:20Z 2018-06-21T08:10:20Z 2005-01-07 Article Journal of Biological Chemistry. Vol.280, No.1 (2005), 677-684 10.1074/jbc.M408438200 00219258 2-s2.0-12844284573 https://repository.li.mahidol.ac.th/handle/123456789/16385 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=12844284573&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Biochemistry, Genetics and Molecular Biology
spellingShingle Biochemistry, Genetics and Molecular Biology
Jong So Kim
Steven L. Coon
Seth Blackshaw
Constance L. Cepko
Morten Møller
Sujira Mukda
Wan Qian Zhao
Clivel G. Charlton
David C. Klein
Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression
description (S)-Adenosylmethionine (SAM) is a critical element of melatonin synthesis as the methyl donor in the last step of the pathway, the O-methylation of N-acetyl 5-hydroxytryptamine by hydroxyindole-O-methyltransferase. The activity of the enzyme that synthesizes SAM, methionine adenosyltransferase (MAT), increases 2.5-fold at night in the pineal gland. In this study, we found that pineal MAT2A mRNA and the protein it encodes, MAT II, also increase at night, suggesting that the increase in MAT activity is caused by an increase in MAT II gene products. The night levels of MAT2A mRNA in the pineal gland were severalfold higher than in other neural and non-neural tissues examined, consistent with the requirement for SAM in melatonin synthesis. Related studies indicate that the nocturnal increase in MAT2A mRNA is caused by activation of a well described neural pathway that mediates photoneural-circadian regulation of the pineal gland. MAT2A mRNA and MAT II protein were increased in organ culture by treatment with norepinephrine (NE), the sympathetic neurotransmitter that stimulates the pineal gland at night. NE is known to markedly elevate pineal cAMP, and here it was found that cAMP agonists elevate MAT2A mRNA levels by increasing MAT2A mRNA synthesis and that drugs that block cAMP activation of cAMP dependent protein kinase block effects of NE. Therefore, the NE-cAMP dependent increase in pineal MAT activity seems to reflect an increase in MAT II protein, which occurs in response to cAMP→protein kinase-dependent increased MAT2A expression. The existence of this MAT regulatory system underscores the importance that MAT plays in melatonin biogenesis. These studies also point to the possibility that SAM production in other tissues might be regulated through cAMP.
author2 National Institute of Child Health and Human Development
author_facet National Institute of Child Health and Human Development
Jong So Kim
Steven L. Coon
Seth Blackshaw
Constance L. Cepko
Morten Møller
Sujira Mukda
Wan Qian Zhao
Clivel G. Charlton
David C. Klein
format Article
author Jong So Kim
Steven L. Coon
Seth Blackshaw
Constance L. Cepko
Morten Møller
Sujira Mukda
Wan Qian Zhao
Clivel G. Charlton
David C. Klein
author_sort Jong So Kim
title Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression
title_short Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression
title_full Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression
title_fullStr Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression
title_full_unstemmed Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression
title_sort methionine adenosyltransferase:adrenergic-camp mechanism regulates a daily rhythm in pineal expression
publishDate 2018
url https://repository.li.mahidol.ac.th/handle/123456789/16385
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