Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat

Štefulj, Jasminka; Hörtner, Michael; Ghosh, Meenakshi; Schauenstein, Konrad; Rinner, I.; Wölfler, Albert; Semmler, Johann; Liebmann, Peter M.

doi:10.1034/j.1600-079x.2001.300408.x

Cited by 208 publications

(151 citation statements)

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“…Nevertheless, in addition to the expected Hiomt expression in goldfish pineal and retina, where MEL synthesis is well documented in vivo and in vitro (Iigo et al, 1991;1997), we found positive signals for HIOMT transcripts in gonads and, to a lesser extent, in liver and gut. These are the first results identifying Hiomt transcripts in non photosensitive organs in fish, and accords with previous studies in rat (Stefulj et al, 2001) and quail (Fu et al, 2001). The high level of gHiomt-2 expression detected in peripheral locations, as gonads, liver, foregut and hindgut support, but do not demonstrate, a local MEL synthesis, and its physiological relevance deserves to be investigated.…”

Section: Distribution Of Aanat-2 and Hiomt-2 Mrna In Goldfishsupporting

confidence: 89%

“…One interesting evidences from present results is the peripheral expression of both enzymes, AANAT-2 and HIOMT-2, which supports MEL synthesis in such peripheral locations. Peripheral AANAT expression has been reported in rodents (Gauer et al, 1999: Stefulj et al, 2001, birds (Kato et al, 1999) and frogs (Isorna et al, 2006). Evidences for AANAT-2 expression in fish was reported in rainbow trout peripheral tissues (Fernández-Durán et al, 2007), but not in others species (pike, trout, zebrafish, Bégay et al, 1998;Coon et al, 1998Coon et al, , 1999Gothilf et al, 1999).…”

Section: Distribution Of Aanat-2 and Hiomt-2 Mrna In Goldfishmentioning

confidence: 99%

“…In fish, low levels of Aanat expression have been detected in the ovary of zebrafish and in different peripheral tissues of rainbow trout (Fernández-Durán et al, 2007). The Hiomt transcripts have been identified in extrapineal and extraretinal locations such as gonad, stomach, gut, skin and immune cells of birds and mammals, suggesting a possible MEL peripheral synthesis (Conti et al, 2000;Fu et al, 2001;Stefulj et al, 2001;Slominski et al, 2008). To date, no data exist about Hiomt expression in extrapineal or extraretinal locations in fish.…”

Section: Introductionmentioning

confidence: 99%

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MELATONIN-SYNTHESIZING ENZYMES IN PINEAL, RETINA, LIVER, AND GUT OF THE GOLDFISH (CARASSIUS): mRNA EXPRESSION PATTERN AND REGULATION OF DAILY RHYTHMS BY LIGHTING CONDITIONS

Velarde

Cerdá‐Reverter

Alonso-Gómez

et al. 2010

Chronobiology International

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(MAX 350 WORDS)Melatonin is currently proposed to be synthesized in non-photosensitive organs of vertebrates, besides its well-known sites of synthesis, the pineal gland and the retina.However, very few studies have demonstrated gene expression of MEL synthesizing enzymes in extrapineal and extraretinal locations. In the present study, present study focuses on the circadian expression of the two key enzymes of the melatoninergic pathway, the AANAT and the HIOMT in central and peripheral locations of the goldfish we give report of the full-length cloning of the two enzymes catalyzing the final steps of melatonin biosynthesis, the arylalkylamine N-acetyltransferase (AANAT) and the hydroxyindole-Omethyltransferase (HIOMT), in a teleosts fish, the goldfish (Carassius auratus). Both enzymes showed high similarity with other teleost sequences, corresponding to the goldfish AANAT-2 and HIOMT-2. Two forms of AANATs were widely known to exist in teleosts, but this is the first time that two isoforms of HIOMT are deduced from a phylogenetic analysis.Both enzymes were detected in several peripheral locations, including liver and gut, being present results the first to find HIOMT in non-photosensitive structures of a fish species. No studies exist on transcriptional regulation of the expression of MEL biosynthesis enzymes in non photosensitive structures in fish The daily expression pattern of both genes in pineal gland, retina, liver and gut was investigated using quantitative real time RT-PCR and cosinor analysis. This is the first time that a rhythmic expression of AANAT and HIOMT are found in digestive tissues of a vertebrate species, supporting a functional melatonin synthesis pathway in liver and gut of the goldfish. Besides, the transcriptional regulation of Aanat-2 in pineal and peripheral locations of goldfish maintained under different lighting conditions was investigated expression of gAANAT-2 is analyzed under different lighting conditions including continuous light and darkness, revealing, as expected, light-dependent rhythms in pineal gland and retina, but also in liver. Nevertheless, the persistence in hindgut of these Aanat-2 rhythms in constant conditions suggests that the expression of this transcript is under circadian clock and entrained by non-photic cues. Our results reinforce the existence of melatonin synthesis in gut and liver of the goldfish, while the rhythmic expression profiles reported point to a regulation of both genes in gut and liver by peripheral oscillators entrainable to non-photic cues.

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Section: Distribution Of Aanat-2 and Hiomt-2 Mrna In Goldfishsupporting

confidence: 89%

Section: Distribution Of Aanat-2 and Hiomt-2 Mrna In Goldfishmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MELATONIN-SYNTHESIZING ENZYMES IN PINEAL, RETINA, LIVER, AND GUT OF THE GOLDFISH (CARASSIUS): mRNA EXPRESSION PATTERN AND REGULATION OF DAILY RHYTHMS BY LIGHTING CONDITIONS

Velarde

Cerdá‐Reverter

Alonso-Gómez

et al. 2010

Chronobiology International

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“…Regarding the immune system, enzymatic machinery expression involved in melatonin synthesis has been demonstrated in lymphoid organs including thymus (Naranjo et al, 2007), bone marrow Conti et al, 2000), peripheral blood mononuclear leucocytes (Pozo et al, 2004) and in human cultured lymphocytes (Carrillo-Vico et al, 2004). Our results confirmed that all extrapineal tissues studied express both necessary key enzymes for melatonin synthesis, as opposed to Stefulj et al, who showed that neither rat immune system (thymus and spleen) nor other peripheral organs (kidney, liver and heart) contain reliable amounts NAT and/or HIOMT (Stefulj et al, 2001). This discrepancy might be due to a different amplification method used (PCR conventional vs. real time PCR).…”

Section: Discussionsupporting

confidence: 91%

Age-related changes in melatonin synthesis in rat extrapineal tissues

Sánchéz-Hidalgo

Lastra

Carrascosa-Salmoral

et al. 2009

Experimental Gerontology

109

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Accepted ManuscriptAge-related changes in melatonin synthesis in rat extrapineal tissues M Sanchez-Hidalgo, C Alarcon de la Lastra, MP Carrascosa-Salmoral, MC Naranjo, A Gomez-Corvera, B Caballero, JM Guerrero PII:S0531-5565 (09) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT AbstractIn the search of new therapeutic targets improving the quality of life of elderly, melatonin, "the chemical expression of darkness", seems to play a remarkable role in aging process possibly due to its antioxidant, immunoenhancer and antiaging properties.The present study was designed to elucidate effects of aging in melatonin extrapineal synthesis and investigate evident age-related alterations in the action mechanisms involved. The presence of the two key enzymes involved in melatonin synthesis, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) was analyzed in thymus, spleen, liver, kidney and heart of 3-and 12 monthold rats using real time PCR as well as its functionality by enzymatic activity assays. In addition, extrapineal melatonin content was measured by a competitive enzyme immunoassay (ELISA). The results of this study reveal that all rat tissues studied including thymus, and for the first time, spleen, liver, kidney and heart have the necessary machinery to synthesize melatonin. Moreover, we report an age-related decline in rat extrapineal melatonin synthesis with a consequent HIOMT functionality decrease in spleen, liver and heart during physiological aging. On the contrary, NAT enzymatic activity maintains unchanged without evident alterations with advancing age.Moreover, diminished melatonin concentrations were measured in these tissues cited above during aging except in the thymus, where, surprisingly, melatonin content, NAT/HIOMT expression, and enzymatic functionality assays revealed no significant alterations with age. As a conclusion, we report evident age-related changes in melatonin synthesis in some rat peripheral organs. We suggest that thymus may develop compensatory mechanisms to counteract the loss of immune activity and consequently, the loss of this potent antioxidant, during physiological aging.

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“…Melatonin (N-acetyl-5-methoxytryptamine), a tryptophan derived small indolic molecule, is mainly secreted by the pineal gland locally in several other tissues (4,5). Experimental evidences proposed the diurnal profiles of blood glucose due to melatonin and increased insulin levels in diabetic animals and humans (6).…”

Section: Introductionmentioning

confidence: 99%

The role of melatonin in diabetes: therapeutic implications

Sharma

Singh

Ahmad

et al. 2015

Arch. Endocrinol. Metab.

107

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Melatonin referred as the hormone of darkness is mainly secreted by pineal gland, its levels being elevated during night and low during the day. The effects of melatonin on insulin secretion are mediated through the melatonin receptors (MT1 and MT2). It decreases insulin secretion by inhibiting cAMP and cGMP pathways but activates the phospholipaseC/IP3 pathway, which mobilizes Ca 2+ from organelles and, consequently increases insulin secretion. Both in vivo and in vitro, insulin secretion by the pancreatic islets in a circadian manner, is due to the melatonin action on the melatonin receptors inducing a phase shift in the cells. Melatonin may be involved in the genesis of diabetes as a reduction in melatonin levels and a functional interrelationship between melatonin and insulin was observed in diabetic patients. Evidences from experimental studies proved that melatonin induces production of insulin growth factor and promotes insulin receptor tyrosine phosphorylation. The disturbance of internal circadian system induces glucose intolerance and insulin resistance, which could be restored by melatonin supplementation. Therefore, the presence of melatonin receptors on human pancreatic islets may have an impact on pharmacotherapy of type 2 diabetes. Arch Endocrinol Metab.2015;59(5):391-9

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Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat

Cited by 208 publications

References 21 publications

MELATONIN-SYNTHESIZING ENZYMES IN PINEAL, RETINA, LIVER, AND GUT OF THE GOLDFISH (CARASSIUS): mRNA EXPRESSION PATTERN AND REGULATION OF DAILY RHYTHMS BY LIGHTING CONDITIONS

MELATONIN-SYNTHESIZING ENZYMES IN PINEAL, RETINA, LIVER, AND GUT OF THE GOLDFISH (CARASSIUS): mRNA EXPRESSION PATTERN AND REGULATION OF DAILY RHYTHMS BY LIGHTING CONDITIONS

Age-related changes in melatonin synthesis in rat extrapineal tissues

The role of melatonin in diabetes: therapeutic implications

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