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Alteration of gene expression profile by melatonin in endothelial cells

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Abstract

Melatonin is secreted by the pineal gland and gastrointestinal tract and plays a role in circadian rhythm synchronization. Melatonin is also reported to have various physiological effects on endothelial cells. Endothelial cells are responsible for physiologic homeostasis and maintaining blood vessel permeability in vivo. In this study, using gene expression profiling, we confirmed about 151 up-regulation and 1,023 downregulation expression genes, with an expression level difference of > 1.5-fold, after exposure to 100 μM and 1 mM melatonin concentrations in endothelial cells. The genes were classified into 16 functional groups based on their functions, including cell adhesion, immune response, lipid metabolism, and response to stress. We analyzed the gene expression profiling data of melatonin-treated human umbilical vein endothelial cells (HUVECs), which indicated a broad spectrum of physiological functions, including anti-oxidative/anti-inflammatory effects and cell-to-cell junction maintenancerelated genes.

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References

  1. Bottaro, D., Shepro, D. & Hechtman, H.B. Heterogeneity of intimal and microvessel endothelial cell barriers in vitro. Microvasc. Res. 32, 389–398 (1986).

    Article  CAS  Google Scholar 

  2. Diglio, C.A., Liu, W., Grammas, P., Giacomelli, F. & Wiener, J. Isolation and characterization of cerebral resistance vessel endothelium in culture. Tissue Cell 25, 833–846 (1993).

    Article  CAS  Google Scholar 

  3. Poliseno, L. et al. MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108, 3068–3071 (2006).

    Article  CAS  Google Scholar 

  4. Jaffe, E.A., Nachman, R.L., Becker, C.G. & Minick, C.R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J. Clin. Invest. 52, 2745–2756 (1973).

    Article  CAS  Google Scholar 

  5. Cui, P. et al. Intracellular signaling pathways involved in cell growth inhibition of human umbilical vein endothelial cells by melatonin. J. Pineal. Res. 44, 107–114 (2008).

    CAS  Google Scholar 

  6. Urata, Y. et al. Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells. Free Radic. Biol. Med. 27, 838–847 (1999).

    Article  CAS  Google Scholar 

  7. Shaikh, A.Y., Xu, J., Wu, Y., He, L. & Hsu, C.Y. Melatonin protects bovine cerebral endothelial cells from hyperoxia-induced DNA damage and death. Neurosci. Lett. 229, 193–197 (1997).

    Article  CAS  Google Scholar 

  8. Buyukokuroglu, M.E., Cemek, M., Yurumez, Y., Yavuz, Y. & Aslan, A. Antioxidative role of melatonin in organophosphate toxicity in rats. Cell Biol. Toxicol. 24, 151–158 (2008).

    Article  CAS  Google Scholar 

  9. Maharaj, D.S., Glass, B.D. & Daya, S. Melatonin: new places in therapy. Biosci. Rep. 27, 299–320 (2007).

    Article  CAS  Google Scholar 

  10. Mulder, H., Nagorny, C.L., Lyssenko, V. & Groop, L. Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene. Diabetologia 52, 1240–1249 (2009).

    Article  CAS  Google Scholar 

  11. Kedziora-Kornatowska, K. et al. Melatonin improves oxidative stress parameters measured in the blood of elderly type 2 diabetic patients. J. Pineal. Res. 46, 333–337 (2009).

    Article  CAS  Google Scholar 

  12. Dubocovich, M.L. & Markowska, M. Functional MT1 and MT2 melatonin receptors in mammals. Endocrine 27, 101–110 (2005).

    Article  CAS  Google Scholar 

  13. Vural, H., Sabuncu, T., Arslan, S.O. & Aksoy, N. Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats. J. Pineal. Res. 31, 193–198 (2001).

    Article  CAS  Google Scholar 

  14. Rodriguez, M.I. et al. Chronic melatonin treatment reduces the age-dependent inflammatory process in senescence-accelerated mice. J. Pineal. Res. 42, 272–279 (2007).

    Article  CAS  Google Scholar 

  15. Silvestri, M. & Rossi, G.A. Melatonin: its possible role in the management of viral infections-a brief review. Italian Journal of Pediatrics 39 (2013).

  16. Shaikh, A.Y., Xu, J., Wu, Y.J., He, L. & Hsu, C.Y. Melatonin protects bovine cerebral endothelial cells from hyperoxia-induced DNA damage and death. Neurosci. Lett. 229, 193–197 (1997).

    Article  CAS  Google Scholar 

  17. Wang, Z. et al. Melatonin, a potent regulator of hemeoxygenase-1, reduces cardiopulmonary bypass-induced renal damage in rats. J. Pineal. Res. 46, 248–254 (2009).

    Article  CAS  Google Scholar 

  18. Parfenova, H. et al. Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection. Am., J. Physiol. Cell Physiol. 290, C1399–1410 (2006).

    Article  CAS  Google Scholar 

  19. Noh, E.M. et al. Dimethylsulfoxide (DMSO) induces downregulation of heme oxygenase-1 (HO-1) in HL-60 cells: involvement of HO-1 in HL-60 cell differentiation. BMB Rep. 44, 753–757 (2011).

    Article  CAS  Google Scholar 

  20. Bai, J. et al. The role of melatonin as an antioxidant in human lens epithelial cells. Free Radical Research 47, 635–642 (2013).

    Article  CAS  Google Scholar 

  21. Lissoni, P. et al. Anti-angiogenic activity of melatonin in advanced cancer patients. Neuro Endocrinol. Lett. 22, 45–47 (2001).

    CAS  Google Scholar 

  22. Tengattini, S. et al. Cardiovascular diseases: protective effects of melatonin. J. Pineal. Res. 44, 16–25 (2008).

    CAS  Google Scholar 

  23. Fan, J. & Watanabe, T. Inflammatory reactions in the pathogenesis of atherosclerosis. J. Atheroscler. Thromb. 10, 63–71 (2003).

    Article  CAS  Google Scholar 

  24. Carlos, T.M. et al. Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. Blood 76, 965–970 (1990).

    CAS  Google Scholar 

  25. Wallez, Y. & Huber, P. Endothelial adherens and tight junctions in vascular homeostasis, inflammation and angiogenesis. Biochim. Biophys. Acta 1778, 794–809 (2008).

    Article  CAS  Google Scholar 

  26. Reiter, R.J., Calvo, J.R., Karbownik, M., Qi, W. & Tan, D.X. Melatonin and its relation to the immune system and inflammation. Ann. N. Y. Acad. Sci. 917, 376–386 (2000).

    Article  CAS  Google Scholar 

  27. Rodriguez, C. et al. Regulation of antioxidant enzymes: a significant role for melatonin. J. Pineal. Res. 36, 1–9 (2004).

    Article  CAS  Google Scholar 

  28. Nakao, T. et al. Melatonin ameliorates angiotensin IIinduced vascular endothelial damage via its antioxidative properties. J. Pineal. Res. 55, 287–293 (2013).

    Article  CAS  Google Scholar 

  29. Youn, G.S., Kwon, D.J., Ju, S.M., Choi, S.Y. & Park, J. Curcumin ameliorates TNF-alpha-induced ICAM-1 expression and subsequent THP-1 adhesiveness via the induction of heme oxygenase-1 in the HaCaT cells. BMB Rep. 46, 410–415 (2013).

    Article  CAS  Google Scholar 

  30. Chen, K., Gunter, K. & Maines, M.D. Neurons overexpressing heme oxygenase-1 resist oxidative stressmediated cell death. J. Neurochem. 75, 304–313 (2000).

    Article  CAS  Google Scholar 

  31. Yang, H. et al. Up-regulation of heme oxygenase-1 by korean red ginseng water extract as a cytoprotective effect in human endothelial cells. J. Ginseng Res. 35, 352–359 (2011).

    Article  CAS  Google Scholar 

  32. Willis, D., Moore, A.R., Frederick, R. & Willoughby, D.A. Heme oxygenase: a novel target for the modulation of the inflammatory response. Nat. Med. 2, 87–90 (1996).

    Article  CAS  Google Scholar 

  33. Lee, S.E. et al. Upregulation of heme oxygenase-1 as an adaptive mechanism for protection against crotonaldehyde in human umbilical vein endothelial cells. Toxicology Letters 201, 240–248 (2011).

    Article  CAS  Google Scholar 

  34. Lee, S.E. & Park, Y.S. The role of antioxidant enzymes in adaptive responses to environmental toxicants in vascular disease. Molecular & Cellular Toxicology 9, 95–101 (2013).

    Article  CAS  Google Scholar 

  35. Lee, S.E. & Park, Y.S. Role of lipid peroxidationderived alpha, beta-unsaturated aldehydes in vascular dysfunction. Oxid. Med. Cell. Longev. 2013, 629028 (2013).

    Google Scholar 

  36. Morita, K., Sasaki, H., Furuse, M. & Tsukita, S. Endothelial claudin: Claudin-5/TMVCF constitutes tight junction strands in endothelial cells. Journal of Cell Biology 147, 185–194 (1999).

    Article  CAS  Google Scholar 

  37. Koto, T. et al. Hypoxia disrupts the barrier function of neural blood vessels through changes in the expression of claudin-5 in endothelial cells. Am. J. Pathol. 170, 1389–1397 (2007).

    Article  CAS  Google Scholar 

  38. Morita, K. et al. Expression of claudin-5 in dermal vascular endothelia. Exp. Dermatol. 12, 289–295 (2003).

    Article  CAS  Google Scholar 

  39. Lee, S.E. et al. Fisetin induces Nrf2-mediated HO-1 expression through PKC-delta and p38 in human umbilical vein endothelial cells. Journal of Cellular Biochemistry 112, 2352–2360 (2011).

    Article  CAS  Google Scholar 

  40. Lee, S.E. et al. MicroRNA and gene expression analysis of melatonin-exposed human breast cancer cell lines indicating involvement of the anticancer effect. Journal of Pineal Research 51, 345–352 (2011).

    Article  CAS  Google Scholar 

  41. Lee, S.E. et al. Genome-wide profiling in melatoninexposed human breast cancer cell lines identifies differentially methylated genes involved in the anticancer effect of melatonin. Journal of Pineal Research 54, 80–88 (2013).

    CAS  Google Scholar 

  42. Kim, H.E., Ishihara, A. & Lee, S.G. The effects of Caffeoylserotonin on inhibition of melanogenesis through the downregulation of MITF via the reduction of intracellular cAMP and acceleration of ERK activation in B16 murine melanoma cells. BMB Rep. 45, 724–729 (2012).

    Article  CAS  Google Scholar 

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Correspondence to Yong Seek Park.

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Son, G.W., Kim, GD., Yang, H. et al. Alteration of gene expression profile by melatonin in endothelial cells. BioChip J 8, 91–101 (2014). https://doi.org/10.1007/s13206-014-8204-1

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  • DOI: https://doi.org/10.1007/s13206-014-8204-1

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