Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin A); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing.

Related collections

Most cited references 33

Record: found
Abstract: found
Article: not found

Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin's primary function and evolution in eukaryotes.

Kei-Xian Tan, Xiaoyan Liu, Ricardo S. Corral … (2013)

Mitochondria and chloroplasts are major sources of free radical generation in living organisms. Because of this, these organelles require strong protection from free radicals and associated oxidative stress. Melatonin is a potent free radical scavenger and antioxidant. It meets the criteria as a mitochondrial and chloroplast antioxidant. Evidence has emerged to show that both mitochondria and chloroplasts may have the capacity to synthesize and metabolize melatonin. The activity of arylalkylamine N-acetyltransferase (AANAT), the reported rate-limiting enzyme in melatonin synthesis, has been identified in mitochondria, and high levels of melatonin have also been found in this organelle. From an evolutionary point of view, the precursor of mitochondria probably is the purple nonsulfur bacterium, particularly, Rhodospirillum rubrum, and chloroplasts are probably the descendents of cyanobacteria. These bacterial species were endosymbionts of host proto-eukaryotes and gradually transformed into cellular organelles, that is, mitochondria and chloroplasts, respectively, thereby giving rise to eukaryotic cells. Of special importance, both purple nonsulfur bacteria (R. rubrum) and cyanobacteria synthesize melatonin. The enzyme activities required for melatonin synthesis have also been detected in these primitive species. It is our hypothesis that mitochondria and chloroplasts are the original sites of melatonin synthesis in the early stage of endosymbiotic organisms; this synthetic capacity was carried into host eukaryotes by the above-mentioned bacteria. Moreover, their melatonin biosynthetic capacities have been preserved during evolution. In most, if not in all cells, mitochondria and chloroplasts may continue to be the primary sites of melatonin generation. Melatonin production in other cellular compartments may have derived from mitochondria and chloroplasts. On the basis of this hypothesis, it is also possible to explain why plants typically have higher melatonin levels than do animals. In plants, both chloroplasts and mitochondria likely synthesize melatonin, while animal cells contain only mitochondria. The high levels of melatonin produced by mitochondria and chloroplasts are used to protect these important cellular organelles against oxidative stress and preserve their physiological functions. The superior beneficial effects of melatonin in both mitochondria and chloroplasts have been frequently reported. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

0 comments Cited 186 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

NF-κB Drives the Synthesis of Melatonin in RAW 264.7 Macrophages by Inducing the Transcription of the Arylalkylamine-N-Acetyltransferase (AA-NAT) Gene

Sandra Marcia Muxel, Marco Pires-Lapa, Alex Willian Arantes Monteiro … (2012)

We demonstrate that during inflammatory responses the nuclear factor kappa B (NF-κB) induces the synthesis of melatonin by macrophages and that macrophage-synthesized melatonin modulates the function of these professional phagocytes in an autocrine manner. Expression of a DsRed2 fluorescent reporter driven by regions of the aa-nat promoter, that encodes the key enzyme involved in melatonin synthesis (arylalkylamine-N-acetyltransferase), containing one or two upstream κB binding sites in RAW 264.7 macrophage cell lines was repressed when NF-κB activity was inhibited by blocking its nuclear translocation or its DNA binding activity or by silencing the transcription of the RelA or c-Rel NF-κB subunits. Therefore, transcription of aa-nat driven by NF-κB dimers containing RelA or c-Rel subunits mediates pathogen-associated molecular patterns (PAMPs) or pro-inflammatory cytokine-induced melatonin synthesis in macrophages. Furthermore, melatonin acts in an autocrine manner to potentiate macrophage phagocytic activity, whereas luzindole, a competitive antagonist of melatonin receptors, decreases macrophage phagocytic activity. The opposing functions of NF-κB in the modulation of AA-NAT expression in pinealocytes and macrophages may represent the key mechanism for the switch in the source of melatonin from the pineal gland to immune-competent cells during the development of an inflammatory response.

0 comments Cited 51 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Melatonin improves D-galactose-induced aging effects on behavior, neurogenesis, and lipid peroxidation in the mouse dentate gyrus via increasing pCREB expression.

Daniel B Shin, Yun Jung Choi, MOO-HO WON … (2011)

Melatonin (N-acetyl-5-methoxytryptamine) has multiple functions. In this study, we investigated the effects of melatonin on memory, cell proliferation, and neuroblast differentiation in the dentate gyrus of a mouse model of D-galactose-induced aging. D-galactose was subcutaneously administered to 7-wk-old mice for 10 wk, and age-matched mice were used as controls. Seven weeks after D-galactose administration, vehicle (water) or melatonin (6 mg/L in water) was administered ad libitum to the mice for 3 wk. The administration of D-galactose significantly increased the escape latency compared with that in the control mice on days 1-3. In addition, cells in the subgranular zone and in the granule cell layer of the dentate gyrus showed severe damage (cytoplasmic condensation) in the D-galactose-treated mice. However, melatonin supplementation to these mice for 3 wk significantly ameliorated the D-galactose-induced increase in escape latency and neuronal damage compared with the vehicle-treated group. The administration of melatonin also significantly restored the D-galactose-induced reduction of proliferating cells (Ki67-positive cells) and differentiating neuroblasts (doublecortin-positive neuroblasts) in the dentate gyrus. Furthermore, the administration of melatonin significantly increased Ser133-phosphorylated cyclic AMP response element binding protein in the dentate gyrus. The administration of melatonin significantly reduced D-galactose-induced lipid peroxidation in the dentate gyrus. These results suggest that melatonin may be helpful in reducing age-related phenomena in the brain. © 2011 John Wiley & Sons A/S.

0 comments Cited 42 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 15 March 2016

Publication date (Electronic): 2 March 2016

Volume: 7

Issue: 11

Pages: 11972-11983

Affiliations

¹ Russian Academy of Science, Moscow, Russian Federation, Russia

² Department of Pathology, Ott Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russian Federation, Russia

³ Laboratory of Cell Biology and Pathology, Institute of Bioregulation and Gerontology, St. Petersburg, Russian Federation, Russia

⁴ CRC Scotland and London, United Kingdom

⁵ Division of Immuhistochemistry, B.V. Petrovsky Russian Surgery Research Center, Moscow, Russian Federation, Russia

⁶ Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, Opera di Padre Pio da Pietrelcina, San Giovanni Rotondo (FG), Italy

Author notes

Correspondence to: Igor M. Kvetnoy, igor.kvetnoy@ 123456yandex.ru

Gianluigi Mazzoccoli, g.mazzoccoli@ 123456operapadrepio.it

Article

Publisher ID: 7863

DOI: 10.18632/oncotarget.7863

PMC ID: 4914262

PubMed ID: 26943046

SO-VID: da5303ea-48b9-43f5-97e5-913158b8e65e

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging

Read this article at

Abstract

Related collections

Aging Pathobiology and Therapeutics

Most cited references 33

Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin's primary function and evolution in eukaryotes.

NF-κB Drives the Synthesis of Melatonin in RAW 264.7 Macrophages by Inducing the Transcription of the Arylalkylamine-N-Acetyltransferase (AA-NAT) Gene

Melatonin improves D-galactose-induced aging effects on behavior, neurogenesis, and lipid peroxidation in the mouse dentate gyrus via increasing pCREB expression.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 246

Cited by 13

Most referenced authors 294