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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2017; 63(4): 105-113

BIOLOGICAL EFFECTS AND PROPERTIES OF EUKARYOTIC SIRTUINS

M.S. Stupchuk, T.Yu. Voznesenskaja

    O.O.Bogomoletz Institute of physiology NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz63.04.105


Abstract

Current review summarizes and discusses the properties of specific proteins – sirtuins, that possess mono-ADPribosyltransferase and deacylase activities. The paper represents the latest idea regarding the classification and biological values of sirtuins: their role in the process of cellular aging, apoptosis, protecting against atherosclerosis and cardiovascular disease. We also consider the effect of sirtuins on the metabolism and a universal transcription factor NF-κB, which controls the expression of genes of the immune response, apoptosis and cell cycle. We describe a number of low molecular weight compounds that are able to activate and inhibit the activity of sirtuins and thus simulating their properties.

Keywords: sirtuins; histone deacetylase; mono-ADPribosyltransferase; aging; apoptosis; resveratrol; nicotinamide.

Full text: (PDF, in Ukrainian)

References

  1. Bitterman JL, Chung JH. Metabolic effects of resveratrol: addressing the controversies. Cell Mol Life Sci. 2015; (8):1473-88. CrossRef PubMed
    2.  
  2. Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF. SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell. 2009; 136(1): 62-74. CrossRef PubMed PubMedCentral
    3.  
  3. Pan H, Finkel T. Key proteins and pathways that regulate lifespan. J Biol Chem. 2017;292(16): 6452-60. CrossRef PubMed
    4.  
  4. Baur JA, Ungvari Z, Minor RK, Le Couteur DG, de Cabo R. Are sirtuins viable targets for improving healthspan and lifespan? Nat Rev Drug Discov 2012; 11: 443-61. CrossRef PubMed PubMedCentral
    5.  
  5. van de Ven RA, Santos D, Haigis MC. Mitochondrial Sirtuins and Molecular Mechanisms of Aging.Trends Mol Med. 2017; 23(4): 320-31. CrossRef PubMed
    6.  
  6. Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010; 5: 253-95. CrossRef PubMed PubMedCentral
    7.  
  7. Orlandi I, Stamerra G, Strippoli M, Vai M. During yeast chronological aging resveratrol supplementation results in a short-lived phenotype Sir2-dependent. Redox Biol. 2017; 12: 745-54. CrossRef PubMed PubMedCentral
    8.  
  8. Winnik S, Auwerx J, Sinclair DA, Matter CM. Protective effects of sirtuins in cardiovascular diseases from bench to bedside. Eur Heart J. 2015; 36(48): 3404-12. CrossRef PubMed PubMedCentral
    9.  
  9. Carabetta VJ, Cristea IM. The regulation, function, and detection of protein acetylation in bacteria. J Bacteriol. 2017: 107-17. CrossRef  
  10. Haigis MC, Guarente LP. Mammalian sirtuins - emerging roles in physiology, aging, and calorierestriction. Genes Dev. 2006; 20: 2913-21. CrossRef PubMed
    11.  
  11. Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Canto C, Mottis A,Jo YS, Viswanathan M, Schoonjans K, Guarente L, Auwerx J. The NAD(+)/Sirtuinpathway modulates longevity through activation of mitochondrial UPR and FOXOsignaling. Cell. 2013; 154: 430-41. CrossRef PubMed PubMedCentral
    12.  
  12. Vaziri H, Dessain SK, Eaton EN, Imai SI, Frye RA. hSIR2(SIRT1) functions as an NADdependent p53 deacetylase. Cell. 2001; 107: 149-59. CrossRef  
  13. Brooks CL, Gu W. How does SIRT1 affect metabolism, senescence and cancer? Nat Rev Cancer. 2009; 9: 123-8. CrossRef PubMed PubMedCentral
    14.  
  14. Kapahi P, Kaeberlein M, Hansen M. Dietary restriction and lifespan: Lessons from invertebrate models. Ageing Res Rev. 2016. pii: S1568-1637(16)30288-4.
    15.  
  15. Winnik S, Stein S, Matter CM. SIRT1 – an antiinflammatory pathway at the crossroads between metabolic disease and atherosclerosis. Curr Vasc Pharmacol 2012; 10: 1-3. CrossRef  
  16. Smith DL Jr,McClure JM, Matecic M, Smith JS. Calorie restriction extends the chronological lifespan of Saccharomyces cerevisiae independently of the Sirtuins. Aging Cell. 2007; 6(5): 649-62. CrossRef PubMed
    17.  
  17. Mahajan SS, Leko V, Simon JA, Bedalov A. Sirtuin modulators. Handb Exp Pharmacol. 2011; 206: 241-55. CrossRef PubMed PubMedCentral
    18.  
  18. Carnevale I, Pellegrini L, D'Aquila P, Saladini S, Lococo E, Polletta L, Vernucci E, Foglio E, Coppola S, Sansone L, Passarino G, Bellizzi D, Russo MA, Fini M, Tafani M. SIRT1-SIRT3 Axis Regulates Cellular Response to Oxidative Stress and Etoposide.J Cell Physiol. 2017; 232(7): 1835-44. CrossRef PubMed
    19.  
  19. Bellizzi D, Dato S, Cavalcante P, Covello G, Di Cianni F. Characterization of a bidirectional promoter shared between two human genes related to aging: SIRT3 and PSMD13. Genomics. 2007; 89: 143-50. CrossRef PubMed
    20.  
  20. Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA. 2008; 105: 3374-9. CrossRef PubMed PubMedCentral
    21.  
  21. Rane S, He M, Sayed D, Vashistha H, Malhotra A. Downregulation of miR-199a derepresses hypoxia-inducible factor-1a and sirtuin 1 and recapitulates hypoxia preconditioning in cardiacmyocytes. Circ Res. 2009; 104: 879-86. CrossRef PubMed PubMedCentral
    22.  
  22. Mei Z, Zhang X, Yi J, Huang J, He J, Tao Y. Sirtuins in metabolism, DNA repair and cancerJ Exp Clin Cancer Res. 2016; 35(1): 182-96. CrossRef PubMed PubMedCentral
    23.  
  23. Zhao W, Kruse JP, Tang Y, Jung SY, Qin J, Gu W. Negative regulation of the deacetylase SIRT1 by DBC1. Nature. 2008; 451: 587-90. CrossRef PubMed PubMedCentral
    24.  
  24. Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009; 9: 327-8. CrossRef PubMed PubMedCentral
    25.  
  25. You M, Liang X, Ajmo JM, Ness GC. Involvement of mammalian sirtuin 1 in the action of ethanol in the liver. Am J Physiol Gastrointest Liver Physiol. 2008; 294: G892-8. CrossRef PubMed
    26.  
  26. Moynihan KA, Grimm AA, Plueger MM, Bernal-Mizrachi E, Ford E. Increased dosage of mammalian Sir2 in pancreatic ß cells enhances glucose-stimulated insulin secretion in mice. Cell Metab. 2005; 2: 105-17. CrossRef PubMed
    27.  
  27. Lappas M. Anti-inflammatory properties of sirtuin 6 in human umbilical vein endothelial cells. Mediators Inflamm 2012; 2012: 597514. CrossRef PubMed PubMedCentral
    28.  
  28. Deng CX. SIRT1, is it a tumor promoter or tumor suppressor? Int J Biol Sci. 2009; 5: 147-52. CrossRef PubMed PubMedCentral
    29.  
  29. Vazquez BN, Thackray JK, Serrano L. Sirtuins and DNA damage repair: SIRT7 comes to play. Nucleus. 2017; 8(2): 107-15. CrossRef PubMed PubMedCentral
    30.  
  30. Bai P, Canto C, Oudart H. PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab. 2011; 13: 461-8. CrossRef PubMed PubMedCentral
    31.  
  31. Pogribny IP, Muskhelishvili L, Tryndyak VP The tumor-promoting activity of 2-acetyl-aminofluorene is associated with disruption of the p53 signaling pathway and the balance between apoptosis and cell proliferation. Toxicol Appl Pharmacol. 2009; 235: 305-11. CrossRef PubMed
    32.  
  32. Yamakuchi M, Lowenstein CJ. MiR-34, SIRT1 and p53: the feedback loop. Cell Cycle. 2009; 8: 712-5. CrossRef PubMed
    33.  
  33. You W, Rotili D, Li TM, Kambach C, Meleshin M, Schutkowski M, Chua KF, Mai A, Steegborn C. Structural Basis of Sirtuin 6 Activation by Synthetic Small Molecules. Angew Chem Int Ed Engl. 2017 Jan 19; 56(4): 1007-11. CrossRef PubMed
    34.  
  34. Zhang QJ, Wang Z, Chen HZ, Zhou S, Zheng W, et al. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc Res. 2008; 80: 191-9. CrossRef PubMed PubMedCentral
    35.  
  35. Canto C, Auwerx J. PGC-1a, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol. 2009; 20: 98-105. CrossRef PubMed PubMedCentral
    36.  
  36. Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS ONE. 2008; 3: e2020. CrossRef PubMed PubMedCentral
    37.  
  37. Yue L, Zhao L, Liu H, Li X, Wang B, Guo H, Gao L, Feng D, Qu Y. Adiponectin Protects against Glutamate-Induced Excitotoxicity via Activating SIRT1-Dependent PGC-1a Expression in HT22 Hippocampal Neurons. Oxid Med Cell Longev. 2016; 1: 1-12. CrossRef PubMed PubMedCentral
    38.  
  38. Lin Q, Geng Y, Lin S, Tian Z.Sirtuin1 (SIRT1) Regulates Tumor Necrosis Factor-alpha (TNF-a-Induced) Aquaporin-2 (AQP2) Expression in Renal Medullary Collecting Duct Cells Through Inhibiting the NF-?B Pathway. Med Sci Monit Basic Res. 2016; 22: 165-74. CrossRef PubMed PubMedCentral
    39.  
  39. Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008; 177: 861-70. CrossRef PubMed PubMedCentral
    40.  
  40. Anderson G. Linking the biological underpinnings of depression: Role of mitochondria interactions with melatonin, inflammation, sirtuins, tryptophan catabolites, DNA repair and oxidative and nitrosative stress, with consequences for classification and cognition.Prog Neuropsychopharmacol Biol Psychiatry. 2017; (16): 30383-9.
    41.  
  41. Zhang F, Zhang M, Wang A, Xu M, Wang C, Xu G, Zhang B, Zou X, Zhuge Y. TWEAK increases SIRT1 expression and promotes p53 deacetylation affecting human hepatic stellate cell senescence.Cell Biol Int. 2017; 41(2): 147-54. CrossRef PubMed
    42.  
  42. Erdogan CS, Mørup-Lendal M, Dalgaard LT, Vang O. Sirtuin 1 independent effects of resveratrol in INS-1E ß-cells.Chem Biol Interact. 2017; 264: 52-60. CrossRef PubMed
    43.  
  43. Bordone L, Motta MC, Picard F, Robinson A, Jhala US, et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic ß cells. PLoS Biol. 2006; 4: e31. CrossRef PubMed PubMedCentral
    44.  
  44. Frye RA. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun. 2000; 273: 793-98. CrossRef PubMed
    45.  
  45. Nassir F, Ibdah JA. Sirtuins and nonalcoholic fatty liver disease. World J Gastroenterol. 2016; 22(46): 10084-92. CrossRef PubMed PubMedCentral
    46.  
  46. Zhao D., Yang J., Yang L. Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes. Oxid Med Cell Longev. 2017; 1: 1-12. CrossRef  
  47. Salminen A, Huuskonen J, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. Activation of innate immunity system during aging: NF-?B signaling is the molecular culprit of inflamm-aging. Ageing Res Rev. 2008; 7: 83-105. CrossRef PubMed
    48.  
  48. Ajmo JM, Liang X, Rogers CQ, Pennock B, You M. Resveratrol alleviates alcoholic fatty liver in mice. Am J Physiol Gastrointest Liver Physiol. 2008; 295: G833-42. CrossRef PubMed PubMedCentral
    49.  
  49. Feige JN, Lagouge M, Canto C, Strehle A, Houten SM, et al. Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab. 2008; 8: 347–358. CrossRef PubMed
    50.  
  50. Winnik S, Stein S, Matter CM. SIRT1 – an antiinflammatory pathway at the crossroads between metabolic disease and atherosclerosis. Curr Vasc Pharmacol. 2012; 10: 1-3. CrossRef  
  51. Chen GD, Yu WD, Chen XP. SirT1 activator represses the transcription of TNF-a in THP-1 cells of a sepsis model via deacetylation of H4K16. Mol Med Rep. 2016; 14(6): 5544-50. CrossRef PubMed PubMedCentral
    52.  
  52. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444: 337-42. CrossRef PubMed PubMedCentral
    53.  
  53. Paik JH. FOXOs in the maintenance of vascular homoeostasis. Biochem Soc Trans. 2006; 34: 731-34. CrossRef PubMed
    54.  
  54. Chen Y, Liu H, Zhang H, Liu E, Xu CB, Su X. The sirt1/ NF-kB signaling pathway is involved in regulation of endothelin type B receptors mediated by homocysteine in vascular smooth muscle cells. Biomed Pharmacother. 2016; 84:1979-85. CrossRef PubMed
    55.  
  55. Lin QQ, Geng YW, Jiang ZW, Tian ZJ. SIRT1 regulates lipopolysaccharide-induced CD40 expression in renal medullary collecting duct cells by suppressing the TLR4- NF-?B signaling pathway. Life Sci. 2017; 170: 100-7. CrossRef PubMed
    56.  
  56. Kelly G. A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 1. Altern Med Rev. 2010; 15(3): 245-63. PubMed
    57.  
  57. Gertz M, Nguyen GTT, Fischer F, Suenkel B, Schlicker C. A Molecular Mechanism for Direct Sirtuin Activation by Resveratrol. 2012. PLoS ONE 7(11): e49761. doi:10.1371/journal.pone.0049761. CrossRef  
  58. Farghali H, Kutinová Canová N, Lekic N. SResveratrol and related compounds as antioxidants with an allosteric mechanism of action in epigenetic drug targets. Physiol Res. 2013; 62(1): 1-13. PubMed
    59.  
  59. Zhang M, Pan Y, Dorfman RG, Yin Y, Zhou Q, Huang S, Liu J, Zhao S. Sirtinol promotes PEPCK1 degradation and inhibits gluconeogenesis by inhibiting deacetylase SIRT2.Sci Rep. 2017; 7(1): 7-17. CrossRef PubMed PubMedCentral
    60.  
  60. Hwang ES, Song SB. Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells.Cell Mol Life Sci. 2017; 1: 2527-38. CrossRef  

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