Hardeland, Rüdiger

[["dc.bibliographiccitation.firstpage","139"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","149"],["dc.bibliographiccitation.volume","165"],["dc.contributor.author","Mayo, J. C."],["dc.contributor.author","Sainz, Rosa M."],["dc.contributor.author","Tan, Dun-Xian"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Leon, J."],["dc.contributor.author","Rodriguez, Carmen"],["dc.contributor.author","Reiter, Russel J."],["dc.date.accessioned","2018-11-07T11:02:38Z"],["dc.date.available","2018-11-07T11:02:38Z"],["dc.date.issued","2005"],["dc.description.abstract","Inflammation is a complex phenomenon involving multiple cellular and molecular interactions which must be tightly regulated. Cyclooxygenase-2 (COX) is the key enzyme that catalyzes the two sequential steps in the biosynthesis of PGs from arachidonic acid. The inducible isoform of COX, namely COX-2, plays a critical role in the inflammatory response and its over-expression has been associated with several pathologies including neurodegenerative diseases and cancer. Melatonin is the main product of the pineal gland with well documented antioxidant and immuno-modulatory effects. Since the action of the indole on COX-2 has not been previously described, the goal of the present report was to test the effect of melatonin on the activities of COX-2 and inducible nitric oxide synthase (NOS), using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as a model. Melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), prevented COX-2 activation induced by LPS, without affecting COX-1 protein levels. The structurally reviewed compound 6-methoxy-melatonin only partially prevented the increase in COX-2 protein levels induced by the toxin. Likewise melatonin prevented NOS activation and reduced the concentration of products from both enzymes, PGE(2) and nitric oxide. Another energenous antioxidant like N-acetyl-cysteine (NAC) did not reduced COX-2 significantly. The current finding corroborates a role of melatonin as an anti-inflammatory agent and, for the first time, COX-2 and NOS as molecular targets for either melatonin or its metabolites AFM - and AMK. These anti-inflammatory actions seem not to be exclusively mediated by the free radical scavenging properties of melatonin. As a consequence, the present work suggests these substances as a new class of potential anti-inflammatory agents without the classical side effects due to COX-1 inhibition. (C) 2005 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jneuroim.2005.05.002"],["dc.identifier.isi","000230995800015"],["dc.identifier.pmid","15975667"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51426"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0165-5728"],["dc.title","Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and n1-acetyl-5-methoxykynuramine (AMK), in macrophages"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2294"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Tan, Dun-Xian"],["dc.contributor.author","Manchester, Lucien C."],["dc.contributor.author","Burkhardt, S."],["dc.contributor.author","Sainz, Rosa M."],["dc.contributor.author","Mayo, J. C."],["dc.contributor.author","Kohen, R."],["dc.contributor.author","Shohami, E."],["dc.contributor.author","Huo, Y. S."],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Reiter, Russel J."],["dc.date.accessioned","2018-11-07T08:47:58Z"],["dc.date.available","2018-11-07T08:47:58Z"],["dc.date.issued","2001"],["dc.description.abstract","The biogenic amine N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK) was investigated for its potential antioxidative capacity. AFMK is a metabolite generated through either an enzymatic or a chemical reaction pathway from melatonin. The physiological function of AFMK remains unknown. To our knowledge, this report is the first to document the potent antioxidant action of this biogenic amine. Cyclic voltammetry (CV) shows that AFMK donates two electrons at potentials of 456 mV and 668 mV, and therefore it functions as a reductive force. This function contrasts with all other physiological antioxidants that donate a single electron only when they neutralize free radicals. AFMK reduced 8-hydroxydeoxyguanosine formation induced by the incubation of DNA with oxidants significantly. Lipid peroxidation resulting from free radical damage to rat liver homogenates was also prevented by the addition of AFMK. The inhibitory effects of AFMK on both DNA and lipid damage appear to be dose-response related. In cell culture, AFMK efficiently reduced hippocampal neuronal death induced by either hydrogen peroxide, glutamate, or amyloid beta (25-35) peptide. AFMK is a naturally occurring molecule with potent free radical scavenging capacity (donating two electrons/molecule) and thus may be a valuable new antioxidant for preventing and treating free radical-related disorders."],["dc.identifier.isi","000170809900017"],["dc.identifier.pmid","11511530"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21087"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","0892-6638"],["dc.title","N-1-acetyl-N-2-formyl-5-methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","113"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Pineal Research"],["dc.bibliographiccitation.lastpage","121"],["dc.bibliographiccitation.volume","53"],["dc.contributor.author","Tan, Dun-Xian"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Manchester, Lucien C."],["dc.contributor.author","Rosales-Corral, Sergio"],["dc.contributor.author","Coto-Montes, Ana"],["dc.contributor.author","Boga, Jose A."],["dc.contributor.author","Reiter, Russel J."],["dc.date.accessioned","2018-11-07T09:06:51Z"],["dc.date.available","2018-11-07T09:06:51Z"],["dc.date.issued","2012"],["dc.description.abstract","Melatonin was considered to be the sole member of this natural family. The emergence of naturally occurring melatonin isomers (MIs) has opened an exciting new research area. Currently, several MIs have been identified in wine, and these molecules are believed to be synthesized by either yeasts or bacteria. A tentative nomenclature for the MIs is proposed in this article. It will be important to explore whether all organisms have the capacity to synthesize MIs, especially under the conditions of environmental stress. These isomers probably share many of the biological functions of melatonin, but their activities seem to exceed those of melatonin. On basis of the limited available information, it seems that MIs differ in their biosynthetic pathways from melatonin. Especially in those compounds in which the aliphatic side chain is not attached to ring atom 3, the starting material may not be tryptophan. Also, the metabolic pathways of MIs remain unknown. This, therefore, is another promising area of research to explore. It is our hypothesis that MIs would increase the performance of yeasts and probiotic bacteria during the processes of fermentation. Therefore, yeasts producing elevated levels of these isomers might have a superior alcohol tolerance and be able to produce higher levels of alcohol. This can be tested by comparing existing yeast strains differing in alcohol tolerance. Selection for MIs may become a strategy for isolating more resistant yeast and Lactobacillus strains, which can be of interest for industrial alcohol production and quality improvements in bacterially fermented foods such as kimchi."],["dc.identifier.doi","10.1111/j.1600-079X.2012.00979.x"],["dc.identifier.isi","000307548500001"],["dc.identifier.pmid","22332602"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25649"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1600-079X"],["dc.relation.issn","0742-3098"],["dc.title","Emergence of naturally occurring melatonin isomers and their proposed nomenclature"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","75"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Pineal Research"],["dc.bibliographiccitation.lastpage","78"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Tan, Dun-Xian"],["dc.contributor.author","Manchester, Lucien C."],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Lopez-Burillo, S."],["dc.contributor.author","Mayo, J. C."],["dc.contributor.author","Sainz, Rosa M."],["dc.contributor.author","Reiter, Russel J."],["dc.date.accessioned","2018-11-07T10:42:36Z"],["dc.date.available","2018-11-07T10:42:36Z"],["dc.date.issued","2003"],["dc.description.abstract","Melatonin, a derivative of an essential amino acid, tryptophan, was first identified in bovine pineal tissue and subsequently it has been portrayed exclusively as a hormone. Recently accumulated evidence has challenged this concept. Melatonin is present in the earliest life forms and is found in all organisms including bacteria, algae, fungi, plants, insects, and vertebrates including humans. Several characteristics of melatonin distinguish it from a classic hormone such as its direct, non-receptor-mediated free radical scavenging activity. As melatonin is also ingested in foodstuffs such as vegetables, fruits, rice, wheat and herbal medicines, from the nutritional point of view, melatonin can also be classified as a vitamin. It seems likely that melatonin initially evolved as an antioxidant, becoming a vitamin in the food chain, and in multicellular organisms, where it is produced, it has acquired autocoid, paracoid and hormonal properties."],["dc.description.sponsorship","NIA NIH HHS [T32AG00165-13]"],["dc.identifier.doi","10.1034/j.1600-079X.2003.02111.x"],["dc.identifier.isi","000179910500011"],["dc.identifier.pmid","12485375"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46837"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Munksgaard"],["dc.relation.issn","0742-3098"],["dc.title","Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","15858"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.lastpage","15890"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Tan, Dun-Xian"],["dc.contributor.author","Zheng, Xiaodong"],["dc.contributor.author","Kong, Jin"],["dc.contributor.author","Manchester, Lucien C."],["dc.contributor.author","Hardeland, Rüdiger"],["dc.contributor.author","Kim, Seok Joong"],["dc.contributor.author","Xu, X."],["dc.contributor.author","Reiter, Russel J."],["dc.date.accessioned","2018-11-07T09:35:42Z"],["dc.date.available","2018-11-07T09:35:42Z"],["dc.date.issued","2014"],["dc.description.abstract","Melatonin and melatonin isomers exist and/or coexist in living organisms including yeasts, bacteria and plants. The levels of melatonin isomers are significantly higher than that of melatonin in some plants and in several fermented products such as in wine and bread. Currently, there are no reports documenting the presence of melatonin isomers in vertebrates. From an evolutionary point of view, it is unlikely that melatonin isomers do not exist in vertebrates. On the other hand, large quantities of the microbial flora exist in the gut of the vertebrates. These microorganisms frequently exchange materials with the host. Melatonin isomers, which are produced by these organisms inevitably enter the host's system. The origins of melatonin and its isomers can be traced back to photosynthetic bacteria and other primitive unicellular organisms. Since some of these bacteria are believed to be the precursors of mitochondria and chloroplasts these cellular organelles may be the primary sites of melatonin production in animals or in plants, respectively. Phylogenic analysis based on its rate-limiting synthetic enzyme, serotonin N-acetyltransferase (SNAT), indicates its multiple origins during evolution. Therefore, it is likely that melatonin and its isomer are also present in the domain of archaea, which perhaps require these molecules to protect them against hostile environments including extremely high or low temperature. Evidence indicates that the initial and primary function of melatonin and its isomers was to serve as the first-line of defence against oxidative stress and all other functions were acquired during evolution either by the process of adoption or by the extension of its antioxidative capacity."],["dc.identifier.doi","10.3390/ijms150915858"],["dc.identifier.isi","000343109700059"],["dc.identifier.pmid","25207599"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11708"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32448"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mdpi Ag"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Fundamental Issues Related to the Origin of Melatonin and Melatonin Isomers during Evolution: Relation to Their Biological Functions"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1557"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Current Medicinal Chemistry"],["dc.bibliographiccitation.lastpage","1565"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Tan, Dun-Xian"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Manchester, Lucien C."],["dc.contributor.author","Galano, A."],["dc.contributor.author","Reiter, Russel J."],["dc.date.accessioned","2018-11-07T09:42:05Z"],["dc.date.available","2018-11-07T09:42:05Z"],["dc.date.issued","2014"],["dc.description.abstract","Cyclic 3-hydroxymelatonin (C3HOM) is an immediate product of melatonin's interaction with reactive oxygen species. Its presence has been detected in mice, rats and humans. In the current study, the antioxidant capacity and reducing power of this molecule have been systematically studied. C3HOM is found to be a more potent antioxidant than melatonin or vitamin C in terms of its ability to scavenge the hydroxyl radical (HO.) and to recover oxidized horseradish peroxidase to its ground state. The antioxidative mechanism of C3HOM is similar to that of the classic antioxidant, vitamin C, rather than to its precursor melatonin. C3HOM effectively prevents the oxidative degradation of cytochrome C induced by hydrogen peroxide (H2O2). It is speculated that some antioxidative activities of melatonin may be mediated by its metabolite, C3HOM. C3HOM prevents mitochondrial cytochrome C injury and, thus, it is likely to inhibit cellular apoptosis induced by the release of oxidized cytochrome C from mitochondria."],["dc.identifier.isi","000333425700007"],["dc.identifier.pmid","24304286"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33877"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bentham Science Publ Ltd"],["dc.relation.issn","1875-533X"],["dc.relation.issn","0929-8673"],["dc.title","Cyclic-3-hydroxymelatonin (C3HOM), A Potent Antioxidant, Scavenges Free Radicals and Suppresses Oxidative Reactions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","775"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","The International Journal of Biochemistry & Cell Biology"],["dc.bibliographiccitation.lastpage","783"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Burkhardt, S."],["dc.contributor.author","Reiter, Russel J."],["dc.contributor.author","Tan, Dun-Xian"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Cabrera, J. A."],["dc.contributor.author","Karbownik, M."],["dc.date.accessioned","2018-11-07T08:49:02Z"],["dc.date.available","2018-11-07T08:49:02Z"],["dc.date.issued","2001"],["dc.description.abstract","Chromium (Cr) compounds are widely used industrial chemicals and well known carcinogens. Cr(III) was earlier found to induce oxidative damage as documented by examining the levels of 8-hydroxydeoxyguanosine (8-OH-dG), an index for DNA damage, in isolated calf thymus DNA incubated with CrCl3 and H2O,. In the present in vitro study, we compared the ability of the free radical scavengers melatonin, N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK), resveratrol and uric acid to reduce DNA damage induced by Cr(III). Each of these scavengers markedly reduced the DNA damage in a concentration-dependent manner. The concentrations that reduced 8-OH-dG formation by 50% (IC50) were 0.10 muM for both resveratrol and melatonin, and 0.27 muM for AFMK. However, the efficacy of the fourth endogenous antioxidant, i.e. uric acid, in terms of its inhibition of DNA damage in the same in vitro system was about 60-150 times less effective than the other scavengers; the IC50 for uric acid was 15.24 muM. These findings suggest that three of the four antioxidants tested in these studies may have utility in protecting against the environmental pollutant Cr and that the protective effects of these free radical scavengers against Cr(III)-induced carcinogenesis may relate to their direct hydroxyl radical scavenging ability. In the present study, the formation of 8-OH-dG was likely due to a Cr(III)-mediated Fenton-type reaction that generates hydroxyl radicals, which in turn damage DNA. Once formed, 8-OH-dG can mutate eventually leading to cancer; thus the implication is that these antioxidants may reduce the incidence of Cr-related cancers. (C) 2001 Published by Elsevier Science Ltd."],["dc.identifier.doi","10.1016/S1357-2725(01)00052-8"],["dc.identifier.isi","000170072700003"],["dc.identifier.pmid","11404181"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21358"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","1357-2725"],["dc.title","DNA oxidatively damaged by chromium(III) and H2O2 is protected by the antioxidants melatonin, N-1-acetyl-N-2-formyl-5-methoxykynuramine, resveratrol and uric acid"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","23448"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.lastpage","23500"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Angeles Bonmati-Carrion, Maria"],["dc.contributor.author","Arguelles-Prieto, Raquel"],["dc.contributor.author","Jose Martinez-Madrid, Maria"],["dc.contributor.author","Reiter, Russel J."],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Angeles Rol, Maria"],["dc.contributor.author","Antonio Madrid, Juan"],["dc.date.accessioned","2018-11-07T09:31:54Z"],["dc.date.available","2018-11-07T09:31:54Z"],["dc.date.issued","2014"],["dc.description.abstract","Currently, in developed countries, nights are excessively illuminated (light at night), whereas daytime is mainly spent indoors, and thus people are exposed to much lower light intensities than under natural conditions. In spite of the positive impact of artificial light, we pay a price for the easy access to light during the night: disorganization of our circadian system or chronodisruption (CD), including perturbations in melatonin rhythm. Epidemiological studies show that CD is associated with an increased incidence of diabetes, obesity, heart disease, cognitive and affective impairment, premature aging and some types of cancer. Knowledge of retinal photoreceptors and the discovery of melanopsin in some ganglion cells demonstrate that light intensity, timing and spectrum must be considered to keep the biological clock properly entrained. Importantly, not all wavelengths of light are equally chronodisrupting. Blue light, which is particularly beneficial during the daytime, seems to be more disruptive at night, and induces the strongest melatonin inhibition. Nocturnal blue light exposure is currently increasing, due to the proliferation of energy-efficient lighting (LEDs) and electronic devices. Thus, the development of lighting systems that preserve the melatonin rhythm could reduce the health risks induced by chronodisruption. This review addresses the state of the art regarding the crosstalk between light and the circadian system."],["dc.identifier.doi","10.3390/ijms151223448"],["dc.identifier.isi","000346797400111"],["dc.identifier.pmid","25526564"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11710"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31631"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mdpi Ag"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","563"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Experimental Dermatology"],["dc.bibliographiccitation.lastpage","568"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Slominski, Andrzej T."],["dc.contributor.author","Semak, Igor"],["dc.contributor.author","Fischer, Tobias W."],["dc.contributor.author","Kim, Tae-Kang"],["dc.contributor.author","Kleszczyński, Konrad"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Reiter, Russel J."],["dc.date.accessioned","2020-12-10T18:28:40Z"],["dc.date.available","2020-12-10T18:28:40Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1111/exd.13208"],["dc.identifier.issn","0906-6705"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/76373"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Metabolism of melatonin in the skin: Why is it important?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","139"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Pineal Research"],["dc.bibliographiccitation.lastpage","166"],["dc.bibliographiccitation.volume","52"],["dc.contributor.author","Hardeland, Ruediger"],["dc.contributor.author","Madrid, Juan Antonio"],["dc.contributor.author","Tan, Dun-Xian"],["dc.contributor.author","Reiter, Russel J."],["dc.date.accessioned","2018-11-07T09:13:16Z"],["dc.date.available","2018-11-07T09:13:16Z"],["dc.date.issued","2012"],["dc.description.abstract","Evidence is accumulating regarding the importance of circadian core oscillators, several associated factors, and melatonin signaling in the maintenance of health. Dysfunction of endogenous clocks, melatonin receptor polymorphisms, age- and disease-associated declines of melatonin likely contribute to numerous diseases including cancer, metabolic syndrome, diabetes type 2, hypertension, and several mood and cognitive disorders. Consequences of gene silencing, overexpression, gene polymorphisms, and deviant expression levels in diseases are summarized. The circadian system is a complex network of central and peripheral oscillators, some of them being relatively independent of the pacemaker, the suprachiasmatic nucleus. Actions of melatonin on peripheral oscillators are poorly understood. Various lines of evidence indicate that these clocks are also influenced or phase-reset by melatonin. This includes phase differences of core oscillator gene expression under impaired melatonin signaling, effects of melatonin and melatonin receptor knockouts on oscillator mRNAs or proteins. Cross-connections between melatonin signaling pathways and oscillator proteins, including associated factors, are discussed in this review. The high complexity of the multioscillator system comprises alternate or parallel oscillators based on orthologs and paralogs of the core components and a high number of associated factors with varying tissue-specific importance, which offers numerous possibilities for interactions with melatonin. It is an aim of this review to stimulate research on melatonin signaling in peripheral tissues. This should not be restricted to primary signal molecules but rather include various secondarily connected pathways and discriminate between direct effects of the pineal indoleamine at the target organ and others mediated by modulation of oscillators."],["dc.description.sponsorship","RETICEF [RD06/0013/0019, BFU 2010-21945-CO1]"],["dc.identifier.doi","10.1111/j.1600-079X.2011.00934.x"],["dc.identifier.isi","000299934600001"],["dc.identifier.pmid","22034907"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27132"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0742-3098"],["dc.title","Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]