Melatonin and retinoid orphan receptors: Demand for new interpretations after their exclusion as nuclear melatonin receptors
Melatonin and RORs: New interpretations
Keywords:
Circadian, Melatonin, Nuclear Receptors, Retinoid receptors, Sirtuin-1
Abstract
The demonstrated incapability of the retinoic acid receptor-related orphan receptor-α (RORα) to bind melatonin inevitably requires consequences for interpreting numerous reports on actions of this protein as far as it was believed to be a nuclear melatonin receptor. While the synthetic compound CGP 52608 is, in fact, a ligand of RORα, effects obtained with this molecule can no longer be attributed to melatonin. Moreover, the sometimes assumed interplay between melatonin membrane receptors and RORα as nuclear receptors has to be dropped. Conclusions on melatonin’s actions via RORα that were based on a lack of demonstrable involvement of membrane receptors appear to have been precocious. Nevertheless, findings on melatonin uptake into the nucleus may still be taken as a hint for nuclear melatonin receptors, but this would require thorough characterization. Although RORα does not bind melatonin, it is interrelated to the latter in regulatory terms by involvement of cellular circadian oscillators. A mode of action seems to be the upregulation of sirtuin-1 by melatonin, deacetylation of poly ADP ribose polymerase-γ coactivator-1α (PGC-1α) by sirtuin-1, and facilitation of RORα binding to its response element by deacetylated PGC-1α, a route that had been shown to exist in circadian oscillators, thereby enhancing their amplitude.
References
1. Becker-André M, Wiesenberg I, Schaeren-Wiemers N, André E, Missbach M, Saurat JH, Carlberg C (1994) Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily. J. Biol Chem 269: 28531-28534.
2. Wiesenberg I, Missbach M, Kahlen JP, Schräder M, Carlberg C (1995)Transcriptional activation of the nuclear receptor RZRα by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand. Nucleic. Acids Res. 23: 327-333.
3. Steinhilber D, Brungs M, Werz O, Wiesenberg I, Danielsson C, Kahlen JP, Nayeri S, Schräder M, Carlberg, C (1995) The nuclear receptor for melatonin represses 5-lipoxygenase gene expression in human B lymphocytes. J. Biol. Chem. 270: 7037-7040.
4. Carlberg C, Wiesenberg I (1995) The orphan receptor family RZR/ROR, melatonin and 5-lipoxygenase: an unexpected relationship. J. Pineal Res. 18: 171-178.
5. Wiesenberg I, Missbach M, Carlberg C (1998) The potential role of the transcription factor RZR/ROR as a mediator of nuclear melatonin signaling. Restor. Neurol. Neurosci. 12: 143-150.
6. Carlberg C (2000) Gene regulation by melatonin. Ann. NY. Acad. Sci. 917: 387-396.
7. Reppert SM, Weaver DR, Ebisawa T (1994) Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 13: 1177-1185.
8. Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (1995) Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc. Natl. Acad. Sci. USA 92: 8734-8738.
9. Liu C, Weaver DR, Jin X, Shearman LP, Pieschl RL, Gribkoff VK, Reppert SM (1997) Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron 19: 91-102.
10. Jin X, von Gall C, Pieschl RL, Gribkoff VK, Stehle JH, Reppert SM, Weaver DR (2003) Targeted disruption of the mouse Mel1b melatonin receptor. Mol. Cell Bio.l 23: 1054-1060.
11. Becker-André M, Schaeren-Wiemers N, André E, Wiesenberg I, Missbach M, Saurat JH, Carlberg C (1997) Erratum (Correction and Addition) to: Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily. J. Biol. Chem. 272: 16707.
12. Smirnov AN (2001) Nuclear melatonin receptors. Biochemistry (Mosc) 66: 19-26.
13. Hardeland R, Madrid JA, Tan D-X, Reiter RJ (2012) Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling. J. Pineal Res. 52: 139-166.
14. Sato TK, Panda S, Miraglia LJ, Reyes TM, Rudic RD, McNamara P, Naik KA, FitzGerald GA, Kay SA, Hogenesch JB (2004) A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron 43: 527-537.
15. Zhang EE, Kay SA (2010) Clocks not winding down: unravelling circadian networks. Nat. Rev. Mol. Cell Biol. 11: 764-776.
16. Chang H-C, Guarente L (2013) SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153: 1448-1460.
17. Hardeland R (2017) Melatonin and the pathologies of weakened or dysregulated circadian oscillators. J. Pineal Res. 62: e12377; DOI: 10.1111/jpi.12377.
18. Bitsch F, Aichholz R, Kallen J, Geisse S, Fournier B, Schlaeppi JM (2003) Identification of natural ligands of retinoic acid receptor-related orphan receptor alpha ligand-binding domain expressed in Sf9 cells – a mass spectrometry approach. Anal. Biochem. 323: 139-149.
19. Solt LA, Burris TP (2012) Action of RORs and their ligands in (patho)physiology. Trends Endocrinol. Metab. 23: 619-627.
20. Slominski AT, Kim TK, Takeda Y, Janjetovic Z, Brozyna AA, Skobowiat C, Wang J, Postlethwaite A, Li W, Tuckey RC, Jetten AM (2014) RORα and RORγ are expressed in human skin and serve as receptors for endogenously produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D. FASEB J. 28: 2775-2789.
21. Slominski AT, Zmijewski MA, Jetten AM (2016) RORα is not a receptor for melatonin (response to DOI 10.1002/bies.201600018). Bioessays 38: 1193-1194.
22. Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi-Perumal SR (2011) Melatonin – A pleiotropic, orchestrating regulator molecule. Prog. Neurobiol. 93: 350-384.
23. Moretti RM, Marelli MM, Motta M, Polizzi D, Monestiroli S, Pratesi G, Limonta P (2001) Activation of the orphan nuclear receptor RORalpha induces growth arrest in androgen-independent DU 145 prostate cancer cells. Prostate 46: 327-335.
24. Moretti RM, Montagnani Marelli M, Motta M, Limonta P (2001) Oncostatic activity of a thiazolidinedione derivative on human androgen-dependent prostate cancer cells. Int. J. Cancer 92: 733-737.
25. Park Y, Hong S, Lee M, Jung H, Cho WJ, Kim EJ, Son HY, Lee MO, Park HG (2012) N-methylthioureas as new agonists of retinoic acid receptor-related orphan receptor. Arch. Pharm. Res. 35: 1393-1401.
26. Missbach M, Jagher B, Sigg I, Nayeri S, Carlberg C, Wiesenberg I (1996) Thiazolidine diones, specific ligands of the nuclear receptor retinoid Z receptor/retinoid acid receptor-related orphan receptor alpha with potent antiarthritic activity. J. Biol. Chem. 271: 13515-13522.
27. Carrillo-Vico A, Lardone PJ, Álvarez-Sánchez N, Rodríguez-Rodríguez A, Guerrero JM (2013) Melatonin: buffering the immune system. Int. J. Mol. Sci.. 14: 8638-8683.
28. Hardeland R (2016) Opposite effects of melatonin in different systems and under different conditions. Curr. Top. Biochem. Res. 17: 57-69.
29. Maestroni GJM, Cardinali DP, Esquifino AI, Pandi-Perumal SR (2005) Does melatonin play a disease-promoting role in rheumatoid arthritis? J. Neuroimmunol. 158: 106-111.
30. Maestroni GJM, Otsa K, Cutolo M (2008) Melatonin treatment does not improve rheumatoid arthritis. Br. J. Clin. Pharmacol.. 65: 797-798.
31. Owen GI, Zelent A (2000) Origins and evolutionary diversification of the nuclear receptor superfamily. Cell. Mol. Life Sci... 57: 809-827.
32. Kolář J, Macháčková I, Johnson CH (1999) Effects of a melatonin analogue CGP 52608 in the photoperiodic flower induction in a short-day plant, Chenopodium rubrum. Biol. Rhythm Res.. 30: 243.
33. Tsim ST, Wong JT, Wong YH (1996) CGP 52608-induced cyst formation in dinoflagellates: possible involvement of a nuclear receptor for melatonin. J. Pineal Res. 21: 101-107.
34. Hardeland R (1999) Melatonin and 5-methoxytryptamine in non-metazoans. Reprod. Nutr. Dev. 39: 399-408.
35. Hardeland R, Pandi-Perumal SR, Poeggeler B (2007) Melatonin in plants – Focus on a vertebrate night hormone with cytoprotective properties. Funct. Plant Sci. Biotechnol.. 1: 32-45.
36. Fuhrberg B, Hardeland R, Poeggeler B, Behrmann G (1997) Dramatic rises of melatonin and 5-methoxytryptamine in Gonyaulax exposed to decreased temperature. Biol. Rhythm Res. 28: 144-150.
37. Balzer I, Hardeland R (1991) Photoperiodism and effects of indoleamines in a unicellular alga, Gonyaulax polyedra. Science 253: 795-797.
38. Karasek M, Pawlikowski M (1999) Antiproliferative effects of melatonin and CGP 52608. Biol. Signals Recept. 8: 75-78.
39. Petranka J, Baldwin W, Biermann J, Jayadev S, Barrett JC, Murphy E (1999)The oncostatic action of melatonin in an ovarian carcinoma cell line. J. Pineal Res. 26: 129-136.
40. Pawlikowski M, Kunert-Radek J, Winczyk K, Melen-Mucha G, Gruszka A, Karasek M (1999) The antiproliferative effects of melatonin on experimental pituitary and colonic tumors. Possible involvement of the putative nuclear binding site? Adv. Exp. Med. Biol. 460: 369-372.
41. Moretti RM, Montagnani Marelli M, Motta M, Limonta P (2002) Role of the orphan nuclear receptor RORα in the control of the metastatic behavior of androgen-independent prostate cancer cells. Oncol. Rep. 9: 1139-1143.
42. Karasek M, Gruszka A, Lawnicka H, Kunert-Radek J, Pawlikowski M (2003) Melatonin inhibits growth of diethylstilbestrol-induced prolactin-secreting pituitary tumor in vitro: possible involvement of nuclear RZR/ROR receptors. J. Pineal Res. 34: 294-296.
43. Herrera F, Mayo JC, Martín V, Sainz RM, Antolin I, Rodriguez C (2004) Cytotoxicity and oncostatic activity of the thiazolidinedione derivative CGP 52608 on central nervous system cancer cells. Cancer Lett. 211: 47-55.
44. Winczyk K, Lawnicka H, Pawlikowski M, Kunert-Radek J, Karasek M (2006) Growth-inhibitory action of melatonin and thiazolidinedione derivative CGP 52608 on murine 16/C breast cancer cells. Neuro. Endocrinol. Lett. 27: 351-354.
45. García-Navarro A, González-Puga C, Escames G, López LC, López A, López-Cantarero M, Camacho E, Espinosa A, Gallo MA, Acuña-Castroviejo D (2007) Cellular mechanisms involved in the melatonin inhibition of HT-29 human colon cancer cell proliferation in culture. J. Pineal Res. 43: 195-205.
46. Hardeland R (2018) Brain inflammaging: roles of melatonin, circadian clocks and sirtuins. J. Clin. Cell Immunol. 9: 543; DOI: 10.4172/2155-9899.1000543.
47. Hardeland R (2018) Recent findings in melatonin research and their relevance to the CNS. Cent Nerv Syst Agents Med. Chem. 18: 102-114.
48. Roberts JE, Wiechmann AF, Hu DN (2000) Melatonin receptors in human uveal melanocytes and melanoma cells. J. Pineal Res. 28: 165-171.
49. Li L, Wong JT, Pang SF, Shiu SY (1999) Melatonin-induced stimulation of rat corpus epididymal epithelial cell proliferation. Life Sci. 65: 1067-1076.
50. Ram PT, Dai J, Yuan L, Dong C, Kiefer TL, Lai L, Hill SM (2002) Involvement of the mt1 melatonin receptor in human breast cancer. Cancer Lett. 179: 141-150.
51. Lardone PJ, Carrillo-Vico A, Molinero P, Rubio A, Guerrero JM (2009) A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production. Cell Mol. Life Sci. 66: 516-525.
52. Moretti RM, Montagnani Marelli M, Sala A, Motta M, Limonta P (2004) Activation of the orphan nuclear receptor RORα counteracts the proliferative effect of fatty acids on prostate cancer cells: crucial role of 5-lipoxygenase. Int. J. Cancer 112: 87-93.
53. Radogna F, Sestili P, Martinelli C, Paolillo M, Paternoster L, Albertini MC, Accorsi A, Gualandi G, Ghibelli L (2009) Lipoxygenase-mediated pro-radical effect of melatonin via stimulation of arachidonic acid metabolism. Toxicol. Appl. Pharmacol. 238: 170-177.
54. Garcia-Mauriño S, Gonzalez-Haba MG, Calvo JR, Rafii-El-Idrissi M, Sanchez-Margalet V, Goberna R, Guerrero JM (1997) Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+ cells: a possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J. Immunol. 159: 574-581.
55. Garcia-Mauriño S, Gonzalez-Haba MG, Calvo JR, Goberna R, Guerrero JM (1998) Involvement of nuclear binding sites for melatonin in the regulation of IL-2 and IL-6 production by human blood mononuclear cells. J. Neuroimmunol. 92: 76-84.
56. García-Mauriño S, Pozo D, Calvo JR, Guerrero JM (2000) Correlation between nuclear melatonin receptor expression and enhanced cytokine production in human lymphocytic and monocytic cell lines. J. Pineal Res. 29: 129-137.
57. Rafii-El-Idrissi M, Calvo JR, Harmouch A, García-Mauriño S, Guerrero JM (1998) Specific binding of melatonin by purified cell nuclei from spleen and thymus of the rat. J. Neuroimmunol. 86: 190-197.
58. Carrillo-Vico A, García-Mauriño S, Calvo JR, Guerrero JM (2003) Melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its mt1 membrane receptor. FASEB J. 17: 755-757.
59. Carrillo-Vico A, García-Pergañeda A, Naji L, Calvo JR, Romero MP, Guerrero JM (2003) Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system. Cell Mol. Life Sci. 60: 2272-2278.
60. Jung-Hynes B, Schmit TL, Reagan-Shaw SR, Siddiqui IA, Mukhtar H, Ahmad N (2011) Melatonin, a novel Sirt1 inhibitor, imparts proliferative effects against prostate cancer cells in vitro culture and in vivo in TRAMP model. J. Pineal Res. 50: 140-149.
61. Hill SM, Frasch T, Xiang S, Duplessis T, Mao L (2009) Molecular mechanisms of melatonin anticancer effects. Integr. Cancer Ther. 8: 337-346.
62. Proietti S, Cucina A, Dobrowolny G, D'Anselmi F, Dinicola S, Masiello MG, Pasqualato A, Palombo A, Morini V, Reiter RJ, Bizzarri M (2014) Melatonin down-regulates MDM2 gene expression and enhances p53 acetylation in MCF-7 cells. J. Pineal Res. 57: 120-129.
63. Hardeland R (2014) Melatonin, noncoding RNAs, messenger RNA stability and epigenetics ― evidence, hints, gaps and perspectives. Int. J. Mol. Sci. 15: 18221-18252.
64. Cristòfol R, Porquet D, Corpas R, Coto-Montes A, Serret J, Camins A, Pallàs M, Sanfeliu C (2012) Neurons from senescence-accelerated SAMP8 mice are protected against frailty by the sirtuin 1 promoting agents melatonin and resveratrol. J. Pineal Res. 52: 271-281.
65. Yu L, Sun Y, Cheng L, Jin Z, Yang Y, Zhai M, Pei H, Wang X, Zhang H, Meng Q, Zhang Y, Yu S, Duan W (2014) Melatonin receptor-mediated protection against myocardial ischemia/reperfusion injury: role of SIRT1. J. Pineal Res. 57: 228-238.
66. Yu L, Liang H, Dong X, Zhao G, Jin Z, Zhai M, Yang Y, Chen W, Liu J, Yi W, Yang J, Yi D, Duan W, Yu S (2015) Reduced silent information regulator 1 signaling exacerbates myocardial ischemia-reperfusion injury in type 2 diabetic rats and the protective effect of melatonin. J. Pineal Res. 59: 376-390.
67. Yang Y, Jiang S, Dong Y, Fan C, Zhao L, Yang X, Li J, Di S, Yue L, Liang G, Reiter RJ, Qu Y (2015) Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice. J. Pineal Res. 58: 61-70.
68. Zhao L, An R, Yang Y, Yang X, Liu H, Yue L, Li X, Lin Y, Reiter RJ, Qu Y (2015) Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation, apoptosis, and oxidative stress: the role of SIRT1 signaling. J. Pineal Res. 59: 230-239.
69. Han D, Huang W, Li X, Gao L, Su T, Li X, Ma S, Liu T, Li C, Chen J, Gao E, Cao F (2016) Melatonin facilitates adipose-derived mesenchymal stem cells to repair the murine infarcted heart via the SIRT1 signaling pathway. J. Pineal Res. 60: 178–192.
70. Bai XZ, He T, Gao JX, Liu Y, Liu JQ, Han SC, Li Y, Shi JH, Han JT, Tao K, Xie ST, Wang HT, Hu DH (2016) Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1. Sci. Rep. 6: 32199; DOI: 10.1038/srep32199.
71. Yang W, Kang X, Qin N, Li F, Jin X, Ma Z, Qian Z, Wu S (2017) Melatonin protects chondrocytes from impairment induced by glucocorticoids via NAD+-dependent SIRT1. Steroids 126: 24-29.
72. Shah SA, Khan M, Jo MH, Jo MG, Amin FU, Kim MO (2017) Melatonin stimulates the SIRT1/Nrf2 signaling pathway counteracting lipopolysaccharide (LPS)-induced oxidative stress to rescue postnatal rat brain. CNS. Neurosci. Ther. 23: 33-44.
73. Peng Z, Zhang W, Qiao J, He B (2018) Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1β in rats with COPD. Int. Immunopharmacol. 62: 23-28.
74. Hardeland R (2018) Extended signaling by melatonin. Cell Cell. Life Sci. J. 3: 000123.
75. Hardeland R (2018) Melatonin and inflammation—Story of a double-edged blade. J. Pineal Res. 65: e12525. DOI: 10.1111/jpi.12525.
76. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P (2009) Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324: 654-657.
77. Bellet MM, Orozco-Solis R, Sahar S, Eckel-Mahan K, Sassone-Corsi P (2011) The time of metabolism: NAD+, SIRT1, and the circadian clock. Cold Spring Harb Symp Quant Biol. 76: 31-38.
78. Sahar S, Sassone-Corsi P (2013) The epigenetic language of circadian clocks. Handb. Exp. Pharmacol. 217: 29-44.
79. Masri S (2015) Sirtuin-dependent clock control: New advances in metabolism, aging and cancer. Curr. Opin. Clin. Nutr. Metab. Care 18: 521-527.
80. Grimaldi B, Nakahata Y, Kaluzova M, Masubuchi S, Sassone-Corsi P (2009) Chromatin remodeling, metabolism and circadian clocks: the interplay of CLOCK and SIRT1. Int. J. Biochem. Cell Biol. 41: 81-86.
81. Andrabi SA, Sayeed I, Siemen D, Wolf G, Horn TF (2004) Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J. 18: 869-871.
82. Hardeland R (2017) Melatonin and the electron transport chain. Cell Mol. Life Sci. 74: 3883-3896.
83. Lemmer B, Labrecque G (1987) Chronopharmacology and chronotherapeutics: definitions and concepts. Chronobiol. Int. 4: 319-329.
84. Reinberg AE (1992) Concepts in chronopharmacology. Annu. Rev. Pharmacol. Toxicol. 32: 51-66.
85. Masana MI, Benloucif S, Dubocovich ML (2000) Circadian rhythm of mt1 melatonin receptor expression in the suprachiasmatic nucleus of the C3H/HeN mouse. J. Pineal Res. 28: 185-192.
86. Pinato L, Ramos D, Hataka A, Rossignoli PS, Granado MD Junior, Mazzetto MC, Campos LMG (2017) Day/night expression of MT1 and MT2 receptors in hypothalamic nuclei of the primate Sapajus apella. J. Chem. Neuroanat. 81: 10-17.
87. Richter HG, Torres-Farfan C, Garcia-Sesnich J, Abarzua-Catalan L, Henriquez MG, Alvarez-Felmer M, Gaete F, Rehren GE, Seron-Ferre M (2008) Rhythmic expression of functional MT1 melatonin receptors in the rat adrenal gland. Endocrinology 149: 995-1003.
88. Venegas C, García JA, Doerrier C, Volt H, Escames G, López LC, Reiter RJ, Acuña-Castroviejo D (2013) Analysis of the daily changes of melatonin receptors in the rat liver. J. Pineal Res. 54: 313-321.
89. Li D, Bi FF, Chen NN, Cao JM, Sun WP, Zhou YM, Li CY, Yang Q (2014) A novel crosstalk between BRCA1 and sirtuin 1 in ovarian cancer. Sci Rep 4, 6666. DOI: 10.1038/srep06666.
90. Aguilar-Arnal L, Sassone-Corsi P (2013) The circadian epigenome: how metabolism talks to chromatin remodeling. Curr. Opin. Cell Biol. 25: 170-176.
91. Luna A, Aladjem MI, Kohn KW (2013) SIRT1/PARP1 crosstalk: connecting DNA damage and metabolism. Genome Integr. 4: 6; DOI: 10.1186/2041-9414-4-6.
92. Mendelsohn AR, Larrick JW (2017) The NAD+/PARP1/SIRT1 axis in aging. Rejuvenation Res. 20: 244-247.
93. Wang S, Yang X, Lin Y, Qiu X, Li H, Zhao X, Cao L, Liu X, Pang Y, Wang X, Chi Z (2013) Cellular NAD depletion and decline of SIRT1 activity play critical roles in PARP-1-mediated acute epileptic neuronal death in vitro. Brain Res. 1535: 14-23.
94. Lopez-Royuela N, Rathore MG, Allende-Vega N, Annicotte JS, Fajas L, Ramachandran B, Gulick T, Villalba M (2014) Extracellular-signal-regulated kinase 5 modulates the antioxidant response by transcriptionally controlling Sirtuin 1 expression in leukemic cells. Int. J. Biochem. Cell Biol. 53: 253-261.
95. Maria S, Samsonraj RM, Munmun F, Glas J, Silvestros M, Kotlarczyk MP, Rylands R, Dudakovic A, van Wijnen AJ, Enderby LT, Lassila H, Dodda B, Davis VL, Balk J, Burow M, Bunnell BA, Witt-Enderby PA (2018) Biological effects of melatonin on osteoblast/osteoclast cocultures, bone, and quality of life: Implications of a role for MT2 melatonin receptors, MEK1/2, and MEK5 in melatonin-mediated osteoblastogenesis. J. Pineal Res. 64: e12465.; DOI: 10.1111/jpi.12465.
96. Antoniali G1, Lirussi L, D'Ambrosio C, Dal Piaz F, Vascotto C, Casarano E, Marasco D, Scaloni A, Fogolari F, Tell G (2014) SIRT1 gene expression upon genotoxic damage is regulated by APE1 through nCaRE-promoter elements. Mol. Biol. Cell 25: 532-547.
97. Hardeland R (2018) Hardeland, R. (2018): On the relationships between lncRNAs and other orchestrating regulators: Role of the circadian system. Epigenomes 2: 9. DOI: 10.3390/epigenomes2020009.
98. Wang GQ, Wang Y, Xiong Y, Chen XC, Ma ML, Cai R, Gao Y, Sun YM, Yang GS, Pang WJ (2016) Sirt1 AS lncRNA interacts with its mRNA to inhibit muscle formation by attenuating function of miR-34a. Sci. Rep. 6: 21865. DOI: 10.1038/srep21865.
99. Tan D, Reiter RJ, Chen LD, Poeggeler B, Manchester LC, Barlow-Walden LR (1994) Both physiological and pharmacological levels of melatonin reduce DNA adduct formation induced by the carcinogen safrole. Carcinogenesis 15: 215-218.
100. Karbownik M, Tan D-X, Reiter RJ (2000) Melatonin reduces the oxidation of nuclear DNA and membrane lipids induced by the carcinogen δ-aminolevulinic acid. Int. J. Cancer 88: 7-11.
101. Menendez-Pelaez A, Reiter RJ (1993) Distribution of melatonin in mammalian tissues: the relative importance of nuclear versus cytosolic localization. J. Pineal Res. 15: 59-69.
102. Acuña-Castroviejo D, Pablos MI, Menendez-Pelaez A, Reiter RJ (1993) Melatonin receptors in purified cell nuclei of liver. Res. Commun. Chem. Pathol. Pharmacol. 82: 253-256.
103. Menendez-Pelaez A, Poeggeler B, Reiter RJ, Barlow-Walden L, Pablos MI, Tan D-X (1993) Nuclear localization of melatonin in different mammalian tissues: immunocytochemical and radioimmunoassay evidence. J. Cell Biochem. 53: 373-382.
104. Acuña-Castroviejo D, Reiter RJ, Menéndez-Peláez A, Pablos MI, Burgos A (1994) Characterization of high-affinity melatonin binding sites in purified cell nuclei of rat liver. J. Pineal Res. 16: 100-112.
105. Messner M, Hardeland R, Rodenbeck A, Huether G (1998) Tissue retention and subcellular distribution of continuously infused melatonin in rats under near physiological conditions. J. Pineal Res. 25: 251-259.
106. Messner M, Hardeland R, Rodenbeck A, Huether G. (1999) Effect of continuous melatonin infusions on steady-state plasma melatonin levels, metabolic fate and tissue retention in rats under near physiological conditions. Adv. Exp. Med. Biol. 467: 303-313.
107. Suofu Y, Li W, Jean-Alphonse FG, Jia J, Khattar NK, Li J, Baranov SV, Leronni D, Mihalik AC, He Y, Cecon E, Wehbi VL, Kim J, Heath BE, Baranova OV, Wang X, Gable MJ, Kretz ES, Di Benedetto G, Lezon TR, Ferrando LM, Larkin TM, Sullivan M, Yablonska S, Wang J, Minnigh MB, Guillaumet G, Suzenet F, Richardson RM, Poloyac SM, Stolz DB, Jockers R, Witt-Enderby PA, Carlisle DL, Vilardaga JP, Friedlander RM (2017) Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. Proc. Natl. Acad.. Sci USA 114: E7997-E8006.
108. Escames G, León J, López LC, Acuña-Castroviejo D (2004) Mechanisms of N-methyl-D-aspartate receptor inhibition by melatonin in the rat striatum. J. Neuroendocrinol. 16: 929-935.
109. Macías M, Escames G, Leon J, Coto A, Sbihi Y, Osuna A, Acuña-Castroviejo D (2003) Calreticulin — melatonin. An unexpected relationship. Eur. J. Biochem. 270: 832-840.
2. Wiesenberg I, Missbach M, Kahlen JP, Schräder M, Carlberg C (1995)Transcriptional activation of the nuclear receptor RZRα by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand. Nucleic. Acids Res. 23: 327-333.
3. Steinhilber D, Brungs M, Werz O, Wiesenberg I, Danielsson C, Kahlen JP, Nayeri S, Schräder M, Carlberg, C (1995) The nuclear receptor for melatonin represses 5-lipoxygenase gene expression in human B lymphocytes. J. Biol. Chem. 270: 7037-7040.
4. Carlberg C, Wiesenberg I (1995) The orphan receptor family RZR/ROR, melatonin and 5-lipoxygenase: an unexpected relationship. J. Pineal Res. 18: 171-178.
5. Wiesenberg I, Missbach M, Carlberg C (1998) The potential role of the transcription factor RZR/ROR as a mediator of nuclear melatonin signaling. Restor. Neurol. Neurosci. 12: 143-150.
6. Carlberg C (2000) Gene regulation by melatonin. Ann. NY. Acad. Sci. 917: 387-396.
7. Reppert SM, Weaver DR, Ebisawa T (1994) Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 13: 1177-1185.
8. Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (1995) Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc. Natl. Acad. Sci. USA 92: 8734-8738.
9. Liu C, Weaver DR, Jin X, Shearman LP, Pieschl RL, Gribkoff VK, Reppert SM (1997) Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron 19: 91-102.
10. Jin X, von Gall C, Pieschl RL, Gribkoff VK, Stehle JH, Reppert SM, Weaver DR (2003) Targeted disruption of the mouse Mel1b melatonin receptor. Mol. Cell Bio.l 23: 1054-1060.
11. Becker-André M, Schaeren-Wiemers N, André E, Wiesenberg I, Missbach M, Saurat JH, Carlberg C (1997) Erratum (Correction and Addition) to: Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily. J. Biol. Chem. 272: 16707.
12. Smirnov AN (2001) Nuclear melatonin receptors. Biochemistry (Mosc) 66: 19-26.
13. Hardeland R, Madrid JA, Tan D-X, Reiter RJ (2012) Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling. J. Pineal Res. 52: 139-166.
14. Sato TK, Panda S, Miraglia LJ, Reyes TM, Rudic RD, McNamara P, Naik KA, FitzGerald GA, Kay SA, Hogenesch JB (2004) A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron 43: 527-537.
15. Zhang EE, Kay SA (2010) Clocks not winding down: unravelling circadian networks. Nat. Rev. Mol. Cell Biol. 11: 764-776.
16. Chang H-C, Guarente L (2013) SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153: 1448-1460.
17. Hardeland R (2017) Melatonin and the pathologies of weakened or dysregulated circadian oscillators. J. Pineal Res. 62: e12377; DOI: 10.1111/jpi.12377.
18. Bitsch F, Aichholz R, Kallen J, Geisse S, Fournier B, Schlaeppi JM (2003) Identification of natural ligands of retinoic acid receptor-related orphan receptor alpha ligand-binding domain expressed in Sf9 cells – a mass spectrometry approach. Anal. Biochem. 323: 139-149.
19. Solt LA, Burris TP (2012) Action of RORs and their ligands in (patho)physiology. Trends Endocrinol. Metab. 23: 619-627.
20. Slominski AT, Kim TK, Takeda Y, Janjetovic Z, Brozyna AA, Skobowiat C, Wang J, Postlethwaite A, Li W, Tuckey RC, Jetten AM (2014) RORα and RORγ are expressed in human skin and serve as receptors for endogenously produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D. FASEB J. 28: 2775-2789.
21. Slominski AT, Zmijewski MA, Jetten AM (2016) RORα is not a receptor for melatonin (response to DOI 10.1002/bies.201600018). Bioessays 38: 1193-1194.
22. Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi-Perumal SR (2011) Melatonin – A pleiotropic, orchestrating regulator molecule. Prog. Neurobiol. 93: 350-384.
23. Moretti RM, Marelli MM, Motta M, Polizzi D, Monestiroli S, Pratesi G, Limonta P (2001) Activation of the orphan nuclear receptor RORalpha induces growth arrest in androgen-independent DU 145 prostate cancer cells. Prostate 46: 327-335.
24. Moretti RM, Montagnani Marelli M, Motta M, Limonta P (2001) Oncostatic activity of a thiazolidinedione derivative on human androgen-dependent prostate cancer cells. Int. J. Cancer 92: 733-737.
25. Park Y, Hong S, Lee M, Jung H, Cho WJ, Kim EJ, Son HY, Lee MO, Park HG (2012) N-methylthioureas as new agonists of retinoic acid receptor-related orphan receptor. Arch. Pharm. Res. 35: 1393-1401.
26. Missbach M, Jagher B, Sigg I, Nayeri S, Carlberg C, Wiesenberg I (1996) Thiazolidine diones, specific ligands of the nuclear receptor retinoid Z receptor/retinoid acid receptor-related orphan receptor alpha with potent antiarthritic activity. J. Biol. Chem. 271: 13515-13522.
27. Carrillo-Vico A, Lardone PJ, Álvarez-Sánchez N, Rodríguez-Rodríguez A, Guerrero JM (2013) Melatonin: buffering the immune system. Int. J. Mol. Sci.. 14: 8638-8683.
28. Hardeland R (2016) Opposite effects of melatonin in different systems and under different conditions. Curr. Top. Biochem. Res. 17: 57-69.
29. Maestroni GJM, Cardinali DP, Esquifino AI, Pandi-Perumal SR (2005) Does melatonin play a disease-promoting role in rheumatoid arthritis? J. Neuroimmunol. 158: 106-111.
30. Maestroni GJM, Otsa K, Cutolo M (2008) Melatonin treatment does not improve rheumatoid arthritis. Br. J. Clin. Pharmacol.. 65: 797-798.
31. Owen GI, Zelent A (2000) Origins and evolutionary diversification of the nuclear receptor superfamily. Cell. Mol. Life Sci... 57: 809-827.
32. Kolář J, Macháčková I, Johnson CH (1999) Effects of a melatonin analogue CGP 52608 in the photoperiodic flower induction in a short-day plant, Chenopodium rubrum. Biol. Rhythm Res.. 30: 243.
33. Tsim ST, Wong JT, Wong YH (1996) CGP 52608-induced cyst formation in dinoflagellates: possible involvement of a nuclear receptor for melatonin. J. Pineal Res. 21: 101-107.
34. Hardeland R (1999) Melatonin and 5-methoxytryptamine in non-metazoans. Reprod. Nutr. Dev. 39: 399-408.
35. Hardeland R, Pandi-Perumal SR, Poeggeler B (2007) Melatonin in plants – Focus on a vertebrate night hormone with cytoprotective properties. Funct. Plant Sci. Biotechnol.. 1: 32-45.
36. Fuhrberg B, Hardeland R, Poeggeler B, Behrmann G (1997) Dramatic rises of melatonin and 5-methoxytryptamine in Gonyaulax exposed to decreased temperature. Biol. Rhythm Res. 28: 144-150.
37. Balzer I, Hardeland R (1991) Photoperiodism and effects of indoleamines in a unicellular alga, Gonyaulax polyedra. Science 253: 795-797.
38. Karasek M, Pawlikowski M (1999) Antiproliferative effects of melatonin and CGP 52608. Biol. Signals Recept. 8: 75-78.
39. Petranka J, Baldwin W, Biermann J, Jayadev S, Barrett JC, Murphy E (1999)The oncostatic action of melatonin in an ovarian carcinoma cell line. J. Pineal Res. 26: 129-136.
40. Pawlikowski M, Kunert-Radek J, Winczyk K, Melen-Mucha G, Gruszka A, Karasek M (1999) The antiproliferative effects of melatonin on experimental pituitary and colonic tumors. Possible involvement of the putative nuclear binding site? Adv. Exp. Med. Biol. 460: 369-372.
41. Moretti RM, Montagnani Marelli M, Motta M, Limonta P (2002) Role of the orphan nuclear receptor RORα in the control of the metastatic behavior of androgen-independent prostate cancer cells. Oncol. Rep. 9: 1139-1143.
42. Karasek M, Gruszka A, Lawnicka H, Kunert-Radek J, Pawlikowski M (2003) Melatonin inhibits growth of diethylstilbestrol-induced prolactin-secreting pituitary tumor in vitro: possible involvement of nuclear RZR/ROR receptors. J. Pineal Res. 34: 294-296.
43. Herrera F, Mayo JC, Martín V, Sainz RM, Antolin I, Rodriguez C (2004) Cytotoxicity and oncostatic activity of the thiazolidinedione derivative CGP 52608 on central nervous system cancer cells. Cancer Lett. 211: 47-55.
44. Winczyk K, Lawnicka H, Pawlikowski M, Kunert-Radek J, Karasek M (2006) Growth-inhibitory action of melatonin and thiazolidinedione derivative CGP 52608 on murine 16/C breast cancer cells. Neuro. Endocrinol. Lett. 27: 351-354.
45. García-Navarro A, González-Puga C, Escames G, López LC, López A, López-Cantarero M, Camacho E, Espinosa A, Gallo MA, Acuña-Castroviejo D (2007) Cellular mechanisms involved in the melatonin inhibition of HT-29 human colon cancer cell proliferation in culture. J. Pineal Res. 43: 195-205.
46. Hardeland R (2018) Brain inflammaging: roles of melatonin, circadian clocks and sirtuins. J. Clin. Cell Immunol. 9: 543; DOI: 10.4172/2155-9899.1000543.
47. Hardeland R (2018) Recent findings in melatonin research and their relevance to the CNS. Cent Nerv Syst Agents Med. Chem. 18: 102-114.
48. Roberts JE, Wiechmann AF, Hu DN (2000) Melatonin receptors in human uveal melanocytes and melanoma cells. J. Pineal Res. 28: 165-171.
49. Li L, Wong JT, Pang SF, Shiu SY (1999) Melatonin-induced stimulation of rat corpus epididymal epithelial cell proliferation. Life Sci. 65: 1067-1076.
50. Ram PT, Dai J, Yuan L, Dong C, Kiefer TL, Lai L, Hill SM (2002) Involvement of the mt1 melatonin receptor in human breast cancer. Cancer Lett. 179: 141-150.
51. Lardone PJ, Carrillo-Vico A, Molinero P, Rubio A, Guerrero JM (2009) A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production. Cell Mol. Life Sci. 66: 516-525.
52. Moretti RM, Montagnani Marelli M, Sala A, Motta M, Limonta P (2004) Activation of the orphan nuclear receptor RORα counteracts the proliferative effect of fatty acids on prostate cancer cells: crucial role of 5-lipoxygenase. Int. J. Cancer 112: 87-93.
53. Radogna F, Sestili P, Martinelli C, Paolillo M, Paternoster L, Albertini MC, Accorsi A, Gualandi G, Ghibelli L (2009) Lipoxygenase-mediated pro-radical effect of melatonin via stimulation of arachidonic acid metabolism. Toxicol. Appl. Pharmacol. 238: 170-177.
54. Garcia-Mauriño S, Gonzalez-Haba MG, Calvo JR, Rafii-El-Idrissi M, Sanchez-Margalet V, Goberna R, Guerrero JM (1997) Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+ cells: a possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J. Immunol. 159: 574-581.
55. Garcia-Mauriño S, Gonzalez-Haba MG, Calvo JR, Goberna R, Guerrero JM (1998) Involvement of nuclear binding sites for melatonin in the regulation of IL-2 and IL-6 production by human blood mononuclear cells. J. Neuroimmunol. 92: 76-84.
56. García-Mauriño S, Pozo D, Calvo JR, Guerrero JM (2000) Correlation between nuclear melatonin receptor expression and enhanced cytokine production in human lymphocytic and monocytic cell lines. J. Pineal Res. 29: 129-137.
57. Rafii-El-Idrissi M, Calvo JR, Harmouch A, García-Mauriño S, Guerrero JM (1998) Specific binding of melatonin by purified cell nuclei from spleen and thymus of the rat. J. Neuroimmunol. 86: 190-197.
58. Carrillo-Vico A, García-Mauriño S, Calvo JR, Guerrero JM (2003) Melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its mt1 membrane receptor. FASEB J. 17: 755-757.
59. Carrillo-Vico A, García-Pergañeda A, Naji L, Calvo JR, Romero MP, Guerrero JM (2003) Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system. Cell Mol. Life Sci. 60: 2272-2278.
60. Jung-Hynes B, Schmit TL, Reagan-Shaw SR, Siddiqui IA, Mukhtar H, Ahmad N (2011) Melatonin, a novel Sirt1 inhibitor, imparts proliferative effects against prostate cancer cells in vitro culture and in vivo in TRAMP model. J. Pineal Res. 50: 140-149.
61. Hill SM, Frasch T, Xiang S, Duplessis T, Mao L (2009) Molecular mechanisms of melatonin anticancer effects. Integr. Cancer Ther. 8: 337-346.
62. Proietti S, Cucina A, Dobrowolny G, D'Anselmi F, Dinicola S, Masiello MG, Pasqualato A, Palombo A, Morini V, Reiter RJ, Bizzarri M (2014) Melatonin down-regulates MDM2 gene expression and enhances p53 acetylation in MCF-7 cells. J. Pineal Res. 57: 120-129.
63. Hardeland R (2014) Melatonin, noncoding RNAs, messenger RNA stability and epigenetics ― evidence, hints, gaps and perspectives. Int. J. Mol. Sci. 15: 18221-18252.
64. Cristòfol R, Porquet D, Corpas R, Coto-Montes A, Serret J, Camins A, Pallàs M, Sanfeliu C (2012) Neurons from senescence-accelerated SAMP8 mice are protected against frailty by the sirtuin 1 promoting agents melatonin and resveratrol. J. Pineal Res. 52: 271-281.
65. Yu L, Sun Y, Cheng L, Jin Z, Yang Y, Zhai M, Pei H, Wang X, Zhang H, Meng Q, Zhang Y, Yu S, Duan W (2014) Melatonin receptor-mediated protection against myocardial ischemia/reperfusion injury: role of SIRT1. J. Pineal Res. 57: 228-238.
66. Yu L, Liang H, Dong X, Zhao G, Jin Z, Zhai M, Yang Y, Chen W, Liu J, Yi W, Yang J, Yi D, Duan W, Yu S (2015) Reduced silent information regulator 1 signaling exacerbates myocardial ischemia-reperfusion injury in type 2 diabetic rats and the protective effect of melatonin. J. Pineal Res. 59: 376-390.
67. Yang Y, Jiang S, Dong Y, Fan C, Zhao L, Yang X, Li J, Di S, Yue L, Liang G, Reiter RJ, Qu Y (2015) Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice. J. Pineal Res. 58: 61-70.
68. Zhao L, An R, Yang Y, Yang X, Liu H, Yue L, Li X, Lin Y, Reiter RJ, Qu Y (2015) Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation, apoptosis, and oxidative stress: the role of SIRT1 signaling. J. Pineal Res. 59: 230-239.
69. Han D, Huang W, Li X, Gao L, Su T, Li X, Ma S, Liu T, Li C, Chen J, Gao E, Cao F (2016) Melatonin facilitates adipose-derived mesenchymal stem cells to repair the murine infarcted heart via the SIRT1 signaling pathway. J. Pineal Res. 60: 178–192.
70. Bai XZ, He T, Gao JX, Liu Y, Liu JQ, Han SC, Li Y, Shi JH, Han JT, Tao K, Xie ST, Wang HT, Hu DH (2016) Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1. Sci. Rep. 6: 32199; DOI: 10.1038/srep32199.
71. Yang W, Kang X, Qin N, Li F, Jin X, Ma Z, Qian Z, Wu S (2017) Melatonin protects chondrocytes from impairment induced by glucocorticoids via NAD+-dependent SIRT1. Steroids 126: 24-29.
72. Shah SA, Khan M, Jo MH, Jo MG, Amin FU, Kim MO (2017) Melatonin stimulates the SIRT1/Nrf2 signaling pathway counteracting lipopolysaccharide (LPS)-induced oxidative stress to rescue postnatal rat brain. CNS. Neurosci. Ther. 23: 33-44.
73. Peng Z, Zhang W, Qiao J, He B (2018) Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1β in rats with COPD. Int. Immunopharmacol. 62: 23-28.
74. Hardeland R (2018) Extended signaling by melatonin. Cell Cell. Life Sci. J. 3: 000123.
75. Hardeland R (2018) Melatonin and inflammation—Story of a double-edged blade. J. Pineal Res. 65: e12525. DOI: 10.1111/jpi.12525.
76. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P (2009) Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324: 654-657.
77. Bellet MM, Orozco-Solis R, Sahar S, Eckel-Mahan K, Sassone-Corsi P (2011) The time of metabolism: NAD+, SIRT1, and the circadian clock. Cold Spring Harb Symp Quant Biol. 76: 31-38.
78. Sahar S, Sassone-Corsi P (2013) The epigenetic language of circadian clocks. Handb. Exp. Pharmacol. 217: 29-44.
79. Masri S (2015) Sirtuin-dependent clock control: New advances in metabolism, aging and cancer. Curr. Opin. Clin. Nutr. Metab. Care 18: 521-527.
80. Grimaldi B, Nakahata Y, Kaluzova M, Masubuchi S, Sassone-Corsi P (2009) Chromatin remodeling, metabolism and circadian clocks: the interplay of CLOCK and SIRT1. Int. J. Biochem. Cell Biol. 41: 81-86.
81. Andrabi SA, Sayeed I, Siemen D, Wolf G, Horn TF (2004) Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J. 18: 869-871.
82. Hardeland R (2017) Melatonin and the electron transport chain. Cell Mol. Life Sci. 74: 3883-3896.
83. Lemmer B, Labrecque G (1987) Chronopharmacology and chronotherapeutics: definitions and concepts. Chronobiol. Int. 4: 319-329.
84. Reinberg AE (1992) Concepts in chronopharmacology. Annu. Rev. Pharmacol. Toxicol. 32: 51-66.
85. Masana MI, Benloucif S, Dubocovich ML (2000) Circadian rhythm of mt1 melatonin receptor expression in the suprachiasmatic nucleus of the C3H/HeN mouse. J. Pineal Res. 28: 185-192.
86. Pinato L, Ramos D, Hataka A, Rossignoli PS, Granado MD Junior, Mazzetto MC, Campos LMG (2017) Day/night expression of MT1 and MT2 receptors in hypothalamic nuclei of the primate Sapajus apella. J. Chem. Neuroanat. 81: 10-17.
87. Richter HG, Torres-Farfan C, Garcia-Sesnich J, Abarzua-Catalan L, Henriquez MG, Alvarez-Felmer M, Gaete F, Rehren GE, Seron-Ferre M (2008) Rhythmic expression of functional MT1 melatonin receptors in the rat adrenal gland. Endocrinology 149: 995-1003.
88. Venegas C, García JA, Doerrier C, Volt H, Escames G, López LC, Reiter RJ, Acuña-Castroviejo D (2013) Analysis of the daily changes of melatonin receptors in the rat liver. J. Pineal Res. 54: 313-321.
89. Li D, Bi FF, Chen NN, Cao JM, Sun WP, Zhou YM, Li CY, Yang Q (2014) A novel crosstalk between BRCA1 and sirtuin 1 in ovarian cancer. Sci Rep 4, 6666. DOI: 10.1038/srep06666.
90. Aguilar-Arnal L, Sassone-Corsi P (2013) The circadian epigenome: how metabolism talks to chromatin remodeling. Curr. Opin. Cell Biol. 25: 170-176.
91. Luna A, Aladjem MI, Kohn KW (2013) SIRT1/PARP1 crosstalk: connecting DNA damage and metabolism. Genome Integr. 4: 6; DOI: 10.1186/2041-9414-4-6.
92. Mendelsohn AR, Larrick JW (2017) The NAD+/PARP1/SIRT1 axis in aging. Rejuvenation Res. 20: 244-247.
93. Wang S, Yang X, Lin Y, Qiu X, Li H, Zhao X, Cao L, Liu X, Pang Y, Wang X, Chi Z (2013) Cellular NAD depletion and decline of SIRT1 activity play critical roles in PARP-1-mediated acute epileptic neuronal death in vitro. Brain Res. 1535: 14-23.
94. Lopez-Royuela N, Rathore MG, Allende-Vega N, Annicotte JS, Fajas L, Ramachandran B, Gulick T, Villalba M (2014) Extracellular-signal-regulated kinase 5 modulates the antioxidant response by transcriptionally controlling Sirtuin 1 expression in leukemic cells. Int. J. Biochem. Cell Biol. 53: 253-261.
95. Maria S, Samsonraj RM, Munmun F, Glas J, Silvestros M, Kotlarczyk MP, Rylands R, Dudakovic A, van Wijnen AJ, Enderby LT, Lassila H, Dodda B, Davis VL, Balk J, Burow M, Bunnell BA, Witt-Enderby PA (2018) Biological effects of melatonin on osteoblast/osteoclast cocultures, bone, and quality of life: Implications of a role for MT2 melatonin receptors, MEK1/2, and MEK5 in melatonin-mediated osteoblastogenesis. J. Pineal Res. 64: e12465.; DOI: 10.1111/jpi.12465.
96. Antoniali G1, Lirussi L, D'Ambrosio C, Dal Piaz F, Vascotto C, Casarano E, Marasco D, Scaloni A, Fogolari F, Tell G (2014) SIRT1 gene expression upon genotoxic damage is regulated by APE1 through nCaRE-promoter elements. Mol. Biol. Cell 25: 532-547.
97. Hardeland R (2018) Hardeland, R. (2018): On the relationships between lncRNAs and other orchestrating regulators: Role of the circadian system. Epigenomes 2: 9. DOI: 10.3390/epigenomes2020009.
98. Wang GQ, Wang Y, Xiong Y, Chen XC, Ma ML, Cai R, Gao Y, Sun YM, Yang GS, Pang WJ (2016) Sirt1 AS lncRNA interacts with its mRNA to inhibit muscle formation by attenuating function of miR-34a. Sci. Rep. 6: 21865. DOI: 10.1038/srep21865.
99. Tan D, Reiter RJ, Chen LD, Poeggeler B, Manchester LC, Barlow-Walden LR (1994) Both physiological and pharmacological levels of melatonin reduce DNA adduct formation induced by the carcinogen safrole. Carcinogenesis 15: 215-218.
100. Karbownik M, Tan D-X, Reiter RJ (2000) Melatonin reduces the oxidation of nuclear DNA and membrane lipids induced by the carcinogen δ-aminolevulinic acid. Int. J. Cancer 88: 7-11.
101. Menendez-Pelaez A, Reiter RJ (1993) Distribution of melatonin in mammalian tissues: the relative importance of nuclear versus cytosolic localization. J. Pineal Res. 15: 59-69.
102. Acuña-Castroviejo D, Pablos MI, Menendez-Pelaez A, Reiter RJ (1993) Melatonin receptors in purified cell nuclei of liver. Res. Commun. Chem. Pathol. Pharmacol. 82: 253-256.
103. Menendez-Pelaez A, Poeggeler B, Reiter RJ, Barlow-Walden L, Pablos MI, Tan D-X (1993) Nuclear localization of melatonin in different mammalian tissues: immunocytochemical and radioimmunoassay evidence. J. Cell Biochem. 53: 373-382.
104. Acuña-Castroviejo D, Reiter RJ, Menéndez-Peláez A, Pablos MI, Burgos A (1994) Characterization of high-affinity melatonin binding sites in purified cell nuclei of rat liver. J. Pineal Res. 16: 100-112.
105. Messner M, Hardeland R, Rodenbeck A, Huether G (1998) Tissue retention and subcellular distribution of continuously infused melatonin in rats under near physiological conditions. J. Pineal Res. 25: 251-259.
106. Messner M, Hardeland R, Rodenbeck A, Huether G. (1999) Effect of continuous melatonin infusions on steady-state plasma melatonin levels, metabolic fate and tissue retention in rats under near physiological conditions. Adv. Exp. Med. Biol. 467: 303-313.
107. Suofu Y, Li W, Jean-Alphonse FG, Jia J, Khattar NK, Li J, Baranov SV, Leronni D, Mihalik AC, He Y, Cecon E, Wehbi VL, Kim J, Heath BE, Baranova OV, Wang X, Gable MJ, Kretz ES, Di Benedetto G, Lezon TR, Ferrando LM, Larkin TM, Sullivan M, Yablonska S, Wang J, Minnigh MB, Guillaumet G, Suzenet F, Richardson RM, Poloyac SM, Stolz DB, Jockers R, Witt-Enderby PA, Carlisle DL, Vilardaga JP, Friedlander RM (2017) Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. Proc. Natl. Acad.. Sci USA 114: E7997-E8006.
108. Escames G, León J, López LC, Acuña-Castroviejo D (2004) Mechanisms of N-methyl-D-aspartate receptor inhibition by melatonin in the rat striatum. J. Neuroendocrinol. 16: 929-935.
109. Macías M, Escames G, Leon J, Coto A, Sbihi Y, Osuna A, Acuña-Castroviejo D (2003) Calreticulin — melatonin. An unexpected relationship. Eur. J. Biochem. 270: 832-840.
Published
2018-12-03
How to Cite
[1]
Hardeland, R. 2018. Melatonin and retinoid orphan receptors: Demand for new interpretations after their exclusion as nuclear melatonin receptors. Melatonin Research. 1, 1 (Dec. 2018), 78-93. DOI:https://doi.org/https://doi.org/10.32794/mr11250005.
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