Abstract
The protein family of sirtuins and FoXO1 transcription factor have been shown to play significant roles in the aging process. In this study we aimed to investigate the changes in the levels of SIRT2, NFκB and FoXO1 and oxidative parameters of colonic mucosa during aging, and the effects of exogenous melatonin (MLT). A total of twenty-four young (3-months-old) and aged (24 months old) male Wistar rats, divided into control [1 % ethanol—phosphate-buffered saline (PBS), s.c. for 21 days] and melatonin (10 mg kg−1 MLT 1 % ethanol in PBS, s.c. for 21 days) were used in the study. The levels of malondialdehyde (MDA) as a parameter of lipid peroxidation, glutathione, NFkB pathway activation, SIRT2 expression, and FoXO1 transcription factor of colonic mucosa were assayed. The MDA levels and SIRT2 expression in the colonic mucosa were significantly increased in the aged group when compared to the younger group. However, the levels of FoXO1 transcription factor were significantly decreased in the aged group. Melatonin significantly decreased the MDA and SIRT2 expression levels of the colonic mucosa in the aged rats. In conclusion, our findings suggest a suppressive role of melatonin in the aging process of colonic tissue via decreasing SIRT2 expression.
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Afanas’ev I (2011) Reactive oxygen species signaling in cancer: comparison with aging. Aging Dis 2:219–230
Akbulut KG, Gonul B, Akbulut H (2009) The role of melatonin on gastric mucosal cell proliferation and telomerase activity in ageing. J Pineal Res 47:308–312
Akbulut KG, Akbulut H, Akgun N, Gonul B (2012) Melatonin decreases apoptosis in gastric mucosa during aging. Aging Clin Exp Res 24:15–20
Aykac G, Uysal M, Yalcin AS, Koçak-Toker N, Sivas A, Oz H (1985) The effects of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 36:71–76
Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303:2011–2015
Calnan DR, Brunet A (2008) The FoxO code. Oncogene 27:2276–2288
Casini A, Ferrali M, Pompella A, Maellaro E, Comporti M (1986) Lipid peroxidation and cellular damage in extrahepatic tissue of bromobenzene intoxicated mice. Am J Pathol 123:520–531
Chobotova K (2009) Aging and cancer: converging routes to disease prevention. Integr Cancer Ther 8:115–122
Chung HY, Lee EK, Choi YJ, Kim JM, Kim DH, Zou Y, Kim CH, Lee J, Kim HS, Kim ND, Jung JH, Yu BP (2011) Molecular inflammation as an underlying mechanism of the aging process and age-related diseases. J Dent Res 90:830–840
Donmez G (2012) The neurobiology of sirtuins and their role in neurodegeneration. Trends Pharmacol Sci 33:494–501
Ferrara N, Rinaldi B, Corbi G, Conti V, Stiuso P, Boccuti S, Rengo G, Rossi F, Filippelli A (2008) Exercise training promotes SIRT1 activity in aged rats. Rejuvenation Res 11:139–150
Finkel T, Deng CX, Mostoslavsky R (2009) Recent progress in the biology and physiology of sirtuins. Nature 460:587–591
Helenius M, Ha¨nninen M, Lehtinen SK, Salminen A (1996) Aging-induced up-regulation of nuclear binding activities of oxidative stress responsive NF-kB transcription factor in mouse cardiac muscle. J Mol Cell Cardiol 28:487–498
Hill SM, Frasch T, Xiang S, Yuan L, Duplessis T, Mao L (2009) Molecular mechanisms of melatonin anticancer effects. Integr Cancer Ther 8:337–346
Huang H, Tindall DJ (2007) Dynamic FoxO transcription factors. J Cell Sci 120(15):2479–2487
Jung-Hynes B, Nihal M, Zhong W, Ahmad N (2009) Role of sirtuin histone deacetylase SIRT1 in prostate cancer. A target for prostate cancer management via its inhibition? J Biol Chem 284:3823–3832
Jung-Hynes B, Reiter RJ, Ahmad N (2010) Sirtuins, melatonin and circadian rhythms: building a bridge between aging and cancer. J Pineal Res 48:9–19
Jung-Hynes B, Schmit TL, Reagan-Shaw SR, Siddiqui IA, Mukhtar H, Ahmad N (2011) Melatonin, a novel SIRT1 inhibitor, imparts antiproliferative effects against prostate cancer in vitro in culture and in vivo in TRAMP model. J Pineal Res 50:140–149
Kara H, Cevik A, Konar V, Dayangac A, Servi K (2008) Effects of selenium with vitamin E and melatonin on cadm, ium-induced oxidative damage in rat liver and kidneys. Biol Trace Elem Res 125:236–244
Karasek M (2007) Does melatonin play a role in aging processes? J Physiol Pharmacol 58:105–113
Kim HS, Vassilopoulos A, Wang RH, Lahusen T, Xiao Z, Xu X, Li C, Veenstra TD, Li B, Yu H, Ji J, Wang XW, Park SH, Cha YI, Gius D, Deng CX (2011) SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell 20:487–499
Kireev RA, Vara E, Tresguerres JAF (2013) Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats. Biogerontology 14:431–442
Korhonen P, Helenius M, Salminen A (1997) Age-related changes in the regulation of transcription factor NF-kB in rat brain. Neurosci Lett 225:61–64
Li W, Zhang B, Tang I, Cao Q, Wu Y, Wu C, Guo J, Ling EA, Liang F (2007) Sirtuin 2 a mammalian homolog of yeast silent information regulator-2 longevity regulator is an oligidendrigliai protein that decerelates cell differentiation through deacetylating alpha-tubulin. J Neurosci 27:2606–2616
Li Y, Matsumori H, Nakayama Y, Osaki M, Kojima H, Kurimasa A, Ito H, Mori S, Katoh M, Oshimura M, Inoue T (2011) SIRT2 down-regulation in HeLa can induce p53 accumulation via p38 MAPK activation dependent p300 decrease, eventually leading to apoptosis. Genes Cells 16:34–45
Lim HD, Kim YS, Ko SH, Yoon IJ, Cho SG, Chun YH, Choi BJ, Kim EC (2012) Cytoprotective and anti-inflammatory effects of melatonin in hydrogen peroxide-stimulated CHON-001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway. J Pineal Res 53:225–237
Mandir N, FitzGerald AJ, Goodlad RA (2005) Differences I the effects of age on intestinal proliferation, crypt fission and apoptosis on the small intestine and the colon of the rat. Int J Exp Pathol 86:125–130
Maxwell MM, Tomkinson EM, Nobles J, Wizeman JW, Amore AM, Quinti L, Chopra V, Hersch SM, Kazantsev AG (2011) The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein that accumulates in the aging CNS. Hum Mol Genet 20:3986–3996
Michian S, Sinclair D (2007) Sirtuins in mammals: insights into their biological function. Biochem J 404:1–13
O’Mahony F, Alzamora R, Chung H-L, Thomas W, Harvey JB (2009) Genomic priming of the antisecretory response to estrogen in rat distal colon throughout the estrous cycle. Mol Endocrinol 23:1885–1899
Pascua P, Camello-Almaraz C, Camello PJ, Martin-Cano FE, Vara E, Fernandez-Tresguerres JA, Pozo MJ (2011) Melatonin, and to a lesser extent growth hormone, restores colonic smooth muscle physiology in old rats. J Pineal Res 51:405–415
Peck B, Chen CY, Ho KK, Di Fruscia P, Myatt SS, Coombes RC, Fuchter MJ, Hsiao CD, Lam EW (2010) SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. Mol Cancer Ther 9:844–855
Roos CM, Hagler M, Zhang B, Oehler EA, Arghami A, Miller JD (2013) Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice. Am J Physiol Heart Circ Physiol 305:H1428–H1439
Salih DAM, Brunet A (2008) FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol 20:126–136
Salminen A, Kaarniranta K (2010) Insulin/IGF-1 paradox of aging: regulation via AKT/IKK/NF-kB signaling. Cell Signal 22:573–577
Sasaki T, Maier B, Bartke A, Scrable H (2006) Progressive loss of SIRT1 with cell cycle withdrawal. Aging Cell 5:413–422
Tilstra JS, Clauson CL, Niedernhofer LJ, Robbins PD (2011) NF-κB in aging and disease. Aging Dis 2:449–465
Tomobe K, Shinozuka T, Kawashima T, Kawashima-Ohya Y, Nomura Y (2013) Age-related changes of forkhead transcription factor FOXO1 in the liver of senescence-accelerated mouse SAMP8. Arch Gerontol Geriatr 57:417–422
Tresguerres JA, Kireev R, Forman K, Cuesta S, Tresguerres AF, Vara E (2012) Effect of chronic melatonin administration on several physiological parameters from old Wistar rats and SAMP8 mice. Curr Aging Sci 5:242–253
van den Berg R, Haenen GRMM, van den Berg H, Bast A (2001) Transcription factor NF-kB as a potential biomarker for oxidative stress. Br J Nutr 86:S121–S127
Wada-Hiraike O, Imamov O, Hiraike H, Hultenby K, Schwend T, Omoto Y, Warner M, Gustafsson JA (2006) Role of estrogen receptor beta in colonic epithelium. Proc Natl Acad Sci U S A 103:2959–2964
Xiong S, Salazar G, Patrushev N, Alexander RW (2011) FoxO1 Mediates an autofeedback loop regulating SIRT1 expression. J Biol Chem 286:5289–5299
Yu J, Auwerx J (2009) The role of sirtuins in the control of metabolic homeostasis. Ann N Y Acad Sci 1173:E10–E19
Zhao Y, Yang J, Liao W, Liu X, Zhang H, Wang S, Wang D, Feng J, Yu L, Zhu WG (2010) Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol 12:665–675
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This work was partly supported by a grant from Turkish Academy of Sciences (TUBA) and Gazi University (2010-37).
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Akbulut, K.G., Aktas, S.H. & Akbulut, H. The role of melatonin, sirtuin2 and FoXO1 transcription factor in the aging process of colon in male rats. Biogerontology 16, 99–108 (2015). https://doi.org/10.1007/s10522-014-9540-1
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DOI: https://doi.org/10.1007/s10522-014-9540-1