Melatonin synthesis: analysis of the more than 150-fold nocturnal increase in serotonin N-acetyltransferase messenger ribonucleic acid in the rat pineal gland.

Roseboom, Patrick H.; Coon, Steven L.; Baler, Rubén; McCune, Susan K.; Weller, Joan L.; Klein, David C.

doi:10.1210/endo.137.7.8770929

Cited by 249 publications

(132 citation statements)

References 32 publications

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“…Actinomycin D and puromycin were determined to be effective in this experiments because the NE-dependent increase in AANAT mRNA was enhanced by treatment with puromycin and blocked by actinomycin D (Fig. 9A), are previously reported (12). In addition, the NE-induced increase in MAT II protein was blocked by either actinomycin D or puromycin (Fig.…”

Section: Mat2a Mrna: Daily Rhythm and Tissue Expression-asupporting

confidence: 64%

“…RNA was separated on a 1.5% agarose/0.7 M formaldehyde gel, transferred to a charged nylon membrane (Nytran; Schleicher and Schuell) by passive capillary transfer, and cross-linked to the membrane using ultraviolet light. The MAT hybridization probes used were based on the 3Ј untranslated region of MAT1A (nucleotides 1283-1837; GenBank TM accession number X15734) or the 3Ј untranslated region of MAT2A (nucleotides 2827-3348, GenBank TM accession number BC062394); the AANAT probe has been described previously (12). Probes were 32 P-labeled by random priming using a DNA Labeling kit (Amersham Biosciences).…”

Section: Mat2a Mrnamentioning

confidence: 99%

“…Stimulation of melatonin production is known to reflect changes in several elements of melatonin synthesis; the most dramatic are large night/day differences in the activity of the next-to-last enzyme in melatonin synthesis, arylalkylamine Nacetyltransferase (AANAT) (12). These control large changes in melatonin synthesis by controlling the production of N-acetyl 5-hydroxytryptamine.…”

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confidence: 99%

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Methionine Adenosyltransferase:Adrenergic-cAMP Mechanism Regulates a Daily Rhythm in Pineal Expression

Kim

Coon

Blackshaw

et al. 2005

Journal of Biological Chemistry

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(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 cAMP3protein 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 .(S)-Adenosylmethionine (SAM), 1 the universal methyl donor, is synthesized by methionine adenosyltransferase (MAT; EC 2.5.1.6) (1-3). MAT exists in three forms, designated MAT I, MAT II, and MAT III. These three isoforms are the products of two genes (MAT1A and MAT2A) (4). MAT I and MAT III are expressed only in adult liver and are encoded by the MAT1A gene (5). MAT I is a tetramer and MAT III is a dimer of a single ␣1-subunit. In contrast to the restricted distribution of MAT I and III, MAT II is found in fetal hepatic tissue, adult extrahepatic tissues, and some transformed hepatocytes. Encoded by MAT2A, the ␣2 subunit plays the role of catalysis; the entire enzyme comprises only ␣2 or is constructed with regulatory ␤-subunits (6). The function of the ␤-subunit seems to be to down-regulate MAT II activity (7); however, the precise nature of the interaction between the ␣2-and ␤-subunits is still not clear.MAT in the pineal gland is of special interest because synthesis of the hormonal product of this tissue, melatonin, requires SAM at the last step (i.e. the O-methylation of N-acetyl 5-hydroxytryptamine by hydroxyindole-O-methyltransferase) (8 -10). Melatonin synthesis in the pineal increases at night by ϳ10-fold in response to stimulation by a neural pathway th...

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Section: Mat2a Mrna: Daily Rhythm and Tissue Expression-asupporting

confidence: 64%

Section: Mat2a Mrnamentioning

confidence: 99%

mentioning

confidence: 99%

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Methionine Adenosyltransferase:Adrenergic-cAMP Mechanism Regulates a Daily Rhythm in Pineal Expression

Kim

Coon

Blackshaw

et al. 2005

Journal of Biological Chemistry

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“…In this gland, melatonin is synthesized from serotonin via arylalkylamine N-acetyltransferase (AANAT), which produces rate-limiting intermediate N-acetylserotonin (NAS). In rodents, AANAT mRNA content (Roseboom et al, 1996;Uz et al, 2002b) and NAS and melatonin levels (Goto et al, 1989;von Gall et al, 2000) are marked by a circadian rhythm with high levels at night and low or even undetectable levels during the day. Recent findings indicate that the pineal gland also contributes to circadian cocaine sensitization; mice mutant for AANAT, whose pineal glands are incapable of synthesizing NAS and melatonin, do not show diurnal cocaine sensitization (Uz et al, 2002a).…”

Section: Introductionmentioning

confidence: 99%

The Pineal Gland is Critical for Circadian Period1 Expression in the Striatum and for Circadian Cocaine Sensitization in Mice

Akhisaroğlu

Ahmed

et al. 2003

Neuropsychopharmacol

107

106

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Sensitization to psychostimulants can be influenced by circadian rhythms. The pineal gland, the main source of circadian melatonin synthesis, may influence behavioral sensitization to cocaine; mice with normal melatonin rhythms do not get sensitized at night. Clock genes such as Period1 (Per1) show rhythmic region-and strain-dependent expression in the mouse brain, and mice mutant for the Per1 gene lack cocaine sensitization. Here, for the first time we show circadian changes of PER1 protein levels in the mouse striatum, a brain region crucial for the development of locomotor sensitization to cocaine. In male C3H/HeJ mice, we found peak striatal PER1 protein levels during the day; this was preceded by a Per1 mRNA peak 16 h earlier. Pinealectomized mice did not show this circadian pattern. We analyzed circadian cocaine sensitization at times when striatal PER1 protein levels in control mice (naive and sham-pinealectomized) were high and low, respectively. Only mice with circadian changes in striatal Per1 expression showed the night-time absence of cocaine sensitization, whereas pinealectomized mice were without circadian changes in striatal Per1 and were sensitized to cocaine regardless of diurnal rhythm. Our results indicate that both the striatal circadian Per1 expression and diurnal locomotor cocaine sensitization are strongly influenced by pineal products. Since we found evidence for the expression of melatonin receptor mRNA in the striatum, we suggest that further studies on pineal-driven mechanisms will help us better understand the mechanisms of drug abuse and identify novel targets for the prevention and/or treatment of addictions.

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“…La liberación de noradrenalina dentro de la glándula pineal durante la noche estimula la síntesis de melatonina (Drijfhout et al). La activación de receptores b1 adrenérgicos causa un incremento en la expresión del gen que codifica para la arilalquilamina-N-acetiltransferasa (AA-NAT), este proceso inmediatamente produce una aumento en la sínte-sis y secreción de melatonina (Roseboom et al, 1996). En ratas, el acido γ-aminobutírico (GABA) liberado en el PVN está involucrado en la inhibición de la síntesis de melatonina inducida por luz (Kalsbeek et al, 2000), lo cual sugiere que Fig.…”

Section: Introductionunclassified

Controladores del Tiempo y el Envejecimiento: Núcleo Supraquiasmático y Glándula Pineal

et al. 2014

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GUADARRAMA-ORTIZ RESUMEN:El núcleo supraquiasmático (NSQ) es el principal reloj biológico de los mamíferos y sincroniza la actividad de la glándula pineal al ciclo luz-oscuridad a través de una vía polisináptica. El efecto de asa de retroalimentación neuroendocrina se lleva a cabo por la melatonina. El presente trabajo pretende demostrar que la glándula pineal modula la sensibilidad a la luz en el NSQ. Se utilizaron ratas Wistar, y se asignaron a 3 grupos: grupo A (falsa pinealectomía -sham-, sin luz), grupo B (falsa pinealectomía -sham-+ luz) y grupo C al cual se le realizó la pinealectomía + luz, después de la manipulación se sacrifican para realizar inmunohistoquímica para c-Fos y al final conteo celular por técnica de estereología. Se obtuvo una reducción del 46,8% del promedio de células inmunorreactivas a c-Fos en el grupo C en comparación del grupo B. Este trabajo muestra que la sensibilidad a la luz está modulada por la actividad de la glándula pineal.

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Melatonin synthesis: analysis of the more than 150-fold nocturnal increase in serotonin N-acetyltransferase messenger ribonucleic acid in the rat pineal gland.

Cited by 249 publications

References 32 publications

Methionine Adenosyltransferase:Adrenergic-cAMP Mechanism Regulates a Daily Rhythm in Pineal Expression

Methionine Adenosyltransferase:Adrenergic-cAMP Mechanism Regulates a Daily Rhythm in Pineal Expression

The Pineal Gland is Critical for Circadian Period1 Expression in the Striatum and for Circadian Cocaine Sensitization in Mice

Controladores del Tiempo y el Envejecimiento: Núcleo Supraquiasmático y Glándula Pineal

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