The Melatonin-producing System is Fully Functional in Retinal Pigment Epithelium (ARPE-19)

Overview

Journal Mol Cell Endocrinol

Specialties Cell Biology
Endocrinology
Molecular Biology

Date 2009 May 5

PMID 19409957

Citations 21

Authors

Michal A Zmijewski

Trevor W Sweatman

Andrzej T Slominski

Affiliations

Soon will be listed here.

Abstract

Since melatonin production has been documented in extrapineal and extraneuronal tissues, we investigated the expression of molecular elements of the melatoninergic system in human RPE cells (ARPE-19). The expression of key enzymes for melatonin synthesis: tryptophan hydroxylases (TPH1 and TPH2); arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT) was detected in ARPE-19 cells using RT-PCR. TPH1 and AANAT proteins were detected in ARPE by Western blotting, while sequential metabolism of tryptophan, serotonin and N-acetylserotonin to melatonin was shown by RP-HPLC. We also demonstrated, by means of RT-PCR, that ARPE expressed mRNA encoding the melatonin receptors: MT2 (but not MT1), two isoforms of nuclear receptor (RORalpha1 and RORalpha4/RZR1), and quinone oxidoreductase (NQO2). By analogy with other peripheral tissues, for example the skin, the expression of these metabolic elements in RPE cells suggests that the RPE represents an additional source of melatonin in the eye, to regulate local homeostasis and prevent from oxidative damage in intra-, auto- and/or paracrine fashions.

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References

Wiechmann A, Summers J . Circadian rhythms in the eye: the physiological significance of melatonin receptors in ocular tissues. Prog Retin Eye Res. 2008; 27(2):137-60. DOI: 10.1016/j.preteyeres.2007.10.001. View

Fischer T, Scholz G, Knoll B, Hipler U, Elsner P . Melatonin reduces UV-induced reactive oxygen species in a dose-dependent manner in IL-3-stimulated leukocytes. J Pineal Res. 2001; 31(1):39-45. DOI: 10.1034/j.1600-079x.2001.310106.x. View

Siu A, Reiter R, To C . Pineal indoleamines and vitamin E reduce nitric oxide-induced lipid peroxidation in rat retinal homogenates. J Pineal Res. 1999; 27(2):122-8. DOI: 10.1111/j.1600-079x.1999.tb00606.x. View

Martin X, Malina H, Brennan M, Hendrickson P, Lichter P . The ciliary body--the third organ found to synthesize indoleamines in humans. Eur J Ophthalmol. 1992; 2(2):67-72. DOI: 10.1177/112067219200200203. View

Slominski A, Zbytek B, Szczesniewski A, Semak I, Kaminski J, Sweatman T . CRH stimulation of corticosteroids production in melanocytes is mediated by ACTH. Am J Physiol Endocrinol Metab. 2004; 288(4):E701-6. DOI: 10.1152/ajpendo.00519.2004. View

Fischer T, Scholz G, Knoll B, Hipler U, Elsner P . Melatonin suppresses reactive oxygen species induced by UV irradiation in leukocytes. J Pineal Res. 2004; 37(2):107-12. DOI: 10.1111/j.1600-079X.2004.00142.x. View

Tan D, Manchester L, Terron M, Flores L, Tamura H, Reiter R . Melatonin as a naturally occurring co-substrate of quinone reductase-2, the putative MT3 melatonin membrane receptor: hypothesis and significance. J Pineal Res. 2007; 43(4):317-20. DOI: 10.1111/j.1600-079X.2007.00513.x. View

Slominski A, Baker J, Rosano T, Guisti L, Ermak G, Grande M . Metabolism of serotonin to N-acetylserotonin, melatonin, and 5-methoxytryptamine in hamster skin culture. J Biol Chem. 1996; 271(21):12281-6. DOI: 10.1074/jbc.271.21.12281. View

Wiechmann A, Udin S, Rada J . Localization of Mel1b melatonin receptor-like immunoreactivity in ocular tissues of Xenopus laevis. Exp Eye Res. 2004; 79(4):585-94. DOI: 10.1016/j.exer.2004.07.004. View

10.

Wiesenberg I, Missbach M, Carlberg C . The potential role of the transcription factor RZR/ROR as a mediator of nuclear melatonin signaling. Restor Neurol Neurosci. 2003; 12(2-3):143-50. View

11.

Slominski A, Pisarchik A, Semak I, Sweatman T, Wortsman J . Characterization of the serotoninergic system in the C57BL/6 mouse skin. Eur J Biochem. 2003; 270(16):3335-44. DOI: 10.1046/j.1432-1033.2003.03708.x. View

12.

LaVail M . Rod outer segment disk shedding in rat retina: relationship to cyclic lighting. Science. 1976; 194(4269):1071-4. DOI: 10.1126/science.982063. View

13.

Pang S, Yu H, Suen H, Brown G . Melatonin in the retina of rats: a diurnal rhythm. J Endocrinol. 1980; 87(1):89-93. DOI: 10.1677/joe.0.0870089. View

14.

Slominski A, Tobin D, Shibahara S, Wortsman J . Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 2004; 84(4):1155-228. DOI: 10.1152/physrev.00044.2003. View

15.

Rodriguez C, Mayo J, Sainz R, Antolin I, Herrera F, Martin V . Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res. 2003; 36(1):1-9. DOI: 10.1046/j.1600-079x.2003.00092.x. View

16.

Lundmark P, Pandi-Perumal S, Srinivasan V, Cardinali D . Role of melatonin in the eye and ocular dysfunctions. Vis Neurosci. 2007; 23(6):853-62. DOI: 10.1017/S0952523806230189. View

17.

Ivanova T, Iuvone P . Melatonin synthesis in retina: circadian regulation of arylalkylamine N-acetyltransferase activity in cultured photoreceptor cells of embryonic chicken retina. Brain Res. 2003; 973(1):56-63. DOI: 10.1016/s0006-8993(03)02540-x. View

18.

Lissoni P, Brivio O, Brivio F, Barni S, Tancini G, Crippa D . Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma. J Pineal Res. 1996; 21(4):239-42. DOI: 10.1111/j.1600-079x.1996.tb00292.x. View

19.

Leon J, Acuna-Castroviejo D, Sainz R, Mayo J, Tan D, Reiter R . Melatonin and mitochondrial function. Life Sci. 2004; 75(7):765-90. DOI: 10.1016/j.lfs.2004.03.003. View

20.

Dubocovich M . Melatonin is a potent modulator of dopamine release in the retina. Nature. 1983; 306(5945):782-4. DOI: 10.1038/306782a0. View