Melatonin biosynthesis in the thymus of humans and rats

Naranjo, María C.; Guerrero, Juan M.; Rubio, Amalia; Lardone, Patricia Judith; Carrillo-Vico, Antonio; Carrascosa-Salmoral, M. P.; Jiménez-Jorge, Silvia; Arellano, M. V.; Leal-Noval, Santiago R.; Leal, Manuel; Lissén, E; Molinero, Patrocinio

doi:10.1007/s00018-007-6435-1

Cited by 84 publications

(62 citation statements)

References 81 publications

(86 reference statements)

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“…Thus, we suggest that, despite action mechanisms involved in melatonin synthesis fail with advancing age, melatonin may be retained by the thymus from the bloodstream or intracellular space for transport to other organs where it exerts its effects or synthesized by the thymus, or both, counteracting the age-associated alterations. Our results agree with the high melatonin levels described in bone marrow , rat thymus 17 (Naranjo et al, 2007) and those reported by Jimenez-Jorge et al (2005).…”

Section: Discussionsupporting

confidence: 94%

“…Our data reveal, not only the presence of NAT and HIOMT mRNAs in rat thymus, spleen, liver, kidney and heart, but also age-related expression differences of both key 14 melatonin biosynthetic enzymes using the relative quantification method. 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).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Age-related changes in melatonin synthesis in rat extrapineal tissues

Sánchéz-Hidalgo

Lastra

Carrascosa-Salmoral

et al. 2009

Experimental Gerontology

109

View full text Add to dashboard Cite

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“…However, numerous published studies have changed this view, describing many extrapineal tissues, such as retina [200], Harderian gland [201], gut [202], ovary [203,204], immune system [205,206], skin [207], and testes [208], as melatonin synthesizers.…”

Section: Melatoninmentioning

confidence: 99%

Paracrine Regulation of Thyroid-Hormone Synthesis by C Cells

Fernández-Santos¹,

García-Marín²,

Utrilla³

et al. 2012

Thyroid Hormone

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“…A szabad gyökök elleni védekezés és az immunrendszer tevékenységének csökkenése kedvez a jellegzetesen idős-kori megbetegedések fellépésének [38], miközben pinealis peptidek adagolása csökkenti a mortalitást [39]. Egyes kutatók feltételezik a thymus és a tobozmirigy funkcionális egységét [40,41], amit a thymus melatonintermelése is alátámaszt [42].…”

Section: A Tobozmirigy-thymus Kapcsolatokunclassified

A tobozmirigy-csecsemőmirigy rendszer szerepe az autoimmunitás, öregedés és élettartam szabályozásában

Csaba

2016

Orvosi Hetilap

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A csecsemőmirigy (thymus) immunoendokrin szerv, amelynek endokrin elemei által termelt hormonok elsősorban a szerv saját immunelemeire hatnak. Az immunrendszerben központi szerepet tölt be, újszülöttkori eltávolítása az immunrendszer és az egész szervezet összeomlásával jár. A thymus dajkasejtjei a csontvelő-eredetű lymphocytákat szelektálják és a sajátot idegenként felismerő (autoreaktív) sejteket még a thymusban elpusztítják, illetve az ugyancsak thymuseredetű Treg-sejtek a periférián elnyomják. A szerv involúciója már születés után elkezdődik, de csak a serdü-lőkor vége felé válik kifejezetté, mert addig az egyidejű fejlődési folyamatok túlkompenzálják. A pubertás utáni involúció inkább megengedi az autoreaktív sejtek életben maradását, felszaporodását és fokozott működését, ami fokozatosan koptatja, pusztítja a szervezet sejtjeit és sejt közötti állományát, ezzel előidézi az öregedés jelenségét. Az autoreaktív sejtek további fokozott működése okozza az autoimmun betegségeket és vezet a természetes halálhoz is. A thymus involúciója tehát nem a szervezet általános sorvadásának részjelensége, hanem annak okozója, ami az élettartam-pacemaker funkcióban mutatkozik meg. Az öregedés tehát felfogható egy thymusvezérelt lassú autoimmun folyamatnak. A tobozmirigy újszülöttkori eltávolítása a thymus degradációjához, az immunrendszer összeomlá-sához és a szervezet sorvadásához (wasting disease) vezet. A mirigy felnőttkori involúciója a thymus involúciójával párhuzamosan fut, így a két szerv funkcionális egységet képez. Valószínű, hogy a corpus pineale felelős a thymus involúciójáért, ezáltal annak élettartam-meghatározó szerepéért is. Az ismertetett adatok nem bizonyítják a tobozmirigy-csecsemőmirigy rendszer kizárólagos szerepét az öregedés és élettartam meghatározásában, csak felhívják a figyelmet arra, hogy ez a rendszer önmagában is alkalmas a feladat elvégzésére. Orv. Hetil., 2016, 157(27), 1065-1070. Kulcsszavak: tobozmirigy, csecsemőmirigy, öregedés, élettartam, immunitás, autoimmun betegségek, immunszelekció, immunöregedésThe role of the pineal-thymus system in the regulation of autoimmunity, aging and lifespan Thymus is an immunoendocrine organ, the hormones of which mainly influence its own lymphatic elements. It has a central role in the immune system, the neonatal removal causes the collapse of immune system and the whole organism. The thymic nurse cells select the bone marrow originated lymphocytes and destroy the autoreactive ones, while thymus originated Treg cells suppress the autoreactive cells in the periphery. The involution of the organ starts after birth, however, this truly happens in the end of puberty only, as before this it is overcompensated by developmental processes. From the end of adolescence the involution allows the life, proliferation and enhanced functioning of some autoreactive cells, which gradually wear down the cells and intercellular materials, causing the aging. The enhanced and mass function of autoreactive cells lead to the autoimmune diseases and natural death. This means that ...

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Melatonin biosynthesis in the thymus of humans and rats

Cited by 84 publications

References 81 publications

Age-related changes in melatonin synthesis in rat extrapineal tissues

Age-related changes in melatonin synthesis in rat extrapineal tissues

Paracrine Regulation of Thyroid-Hormone Synthesis by C Cells

A tobozmirigy-csecsemőmirigy rendszer szerepe az autoimmunitás, öregedés és élettartam szabályozásában

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