Journal of Physiology and Biochemistry

, Volume 69, Issue 4, pp 957–961 | Cite as

Nephroprotective action of sirtuin 1 (SIRT1)

  • Dorota Polak-Jonkisz
  • Krystyna Laszki-Szcząchor
  • Leopold Rehan
  • Witold Pilecki
  • Henryk Filipowski
  • Małgorzata Sobieszczańska
Mini Review


Sirtuins, silent information regulator 2 (Sir 2) proteins, belong to the family of NAD+-dependent enzymes with deacetylase or mono-ADP-ribosyltransferase activity. These enzymes are responsible for processes of DNA repair or recombination, chromosomal stability and gene transcription. In mammals, sirtuins occur in seven varieties, from 1 to 7 (SIRT1–SIRT7), differing among themselves with location. SIRT1, the best known variety, exerts its effects on proteins via NAD+ coenzymes, being thus associated with cellular energetic metabolism and the ‘red–ox’ state. Its deficits are, among others, concomitant with stressful situations and associated with pathophysiologies of many medical conditions, including diabetes mellitus, cardiovascular diseases, neurodegenerative syndromes and kidney diseases. In kidney disorders, it promotes (stimulates) the survival of cells in an affected kidney by modulating their responses to various stress stimuli, takes part in arterial blood pressure control, protects against cellular apoptosis in renal tubules by catalase induction and triggers autophagy. More and more available in vitro and in vivo data indicate SIRT1 activity to be oriented, among others, towards nephroprotection. Thus, SIRT1 may become a novel element in the therapy of age-related renal diseases, including diabetic nephropathy.


Sirtuins Sirtuin 1 SIRT1 Nephroprotection 





Autophagy protein 5


Autophagy protein 7




Cyclooxygenase-II enzyme


Caloric restriction


Deoxyribonucleic acid


Disruptor of telomeric silencing-1


Epithelial sodium channel


Extracellular signal-regulated kinases


Forkhead box O3


farnesoid X receptor


hypoxia-inducible factor


Protein that, in humans, is encoded by the XRCC6 gene


protein light chain 3


liver X receptor


lysine 310


Nicotinamide adenine dinucleotide


Generating nicotinamide


Nuclear factor kappa B


Nitrogen oxide


prostaglandin E2


angiotensin II receptor, type 1


Silent information regulator


Mothers against decapentaplegic homolog 3


sterol regulatory element binding proteins


Transforming growth factor beta


uncoupling protein 2


  1. 1.
    Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, Czopik A, Steele AD, Crowe H, Marmor S, Luo J (2007) SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6(6):759–767PubMedCrossRefGoogle Scholar
  2. 2.
    Cohen HY, Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305(5682):390–392PubMedCrossRefGoogle Scholar
  3. 3.
    Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasle TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325(5937):201–204PubMedCrossRefGoogle Scholar
  4. 4.
    Hao CH, Haase VH (2010) Sirtuins and their relevance to the kidney. J Am Soc Nephrol 21(10):1620–1627PubMedCrossRefGoogle Scholar
  5. 5.
    Hasegawa K, Wakino S, Yoshioka K, Tatematsu S, Hara Y, Minakuchi H, Washida N, Tokuyama H, Hayashi K, Itoh H (2008) Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression. Biochem Biophys Res Commun 372(1):51–56PubMedCrossRefGoogle Scholar
  6. 6.
    Hasegawa K, Wakino S, Yoshioka K, Tatematsu S, Hara Y, Minakuchi H, Sueyasu K, Washida N, Tokuyama H, Tzukerman M (2010) Kidney-specific overexpression of Sirt1 protects against acute kidney injury by retaining peroxisome function. J Biol Chem 285(17):13045–13056PubMedCrossRefGoogle Scholar
  7. 7.
    He W, Wang Y, Zhang MZ, You L, Davis LS, Fan H, Yang HC, Fogo AB, Zent R, Harris RC (2010) Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest 120(4):1056–1068PubMedCrossRefGoogle Scholar
  8. 8.
    Kitada M, Kume S, Takeda-Watanabe A, Kanasaki K, Koya D (2013) Sirtuins and renal diseases: relationship with aging and diabetic nephropathy. Clin Sci 124(3):153–164PubMedCrossRefGoogle Scholar
  9. 9.
    Kitada M, Takeda A, Nagai T, Ito H, Kanasaki K, Koya D (2011) Dietary restriction ameliorates diabetic nephropathy through anti-inflammatory effects and regulation of the autophagy via restoration of Sirt1 in diabetic Wistar fatty (fa/fa) rats: a model of type 2 diabetes. Exp Diabetes Res 2011:908185PubMedCrossRefGoogle Scholar
  10. 10.
    Kume S, Uzu T, Horiike K, Chin-Kanasaki M, Isshiki K, Araki S, Sugimoto T, Haneda M, Kashiwagi A, Koya D (2010) Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest 120(4):1043–1055PubMedCrossRefGoogle Scholar
  11. 11.
    Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, Tsokos M, Alt FW, Finkel T (2008) A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA 105(9):3374–3379PubMedCrossRefGoogle Scholar
  12. 12.
    Li J, Qu X, Ricardo SD, Bertram JF, Nikolic-Paterson DJ (2010) Resveratrol inhibits renal fibrosis in the obstructed kidney: potential role in deacetylation of Smad3. Am J Pathol 177(3):1065–1071PubMedCrossRefGoogle Scholar
  13. 13.
    Lim JH, Lee YM, Chun YS, Chen J, Kim JE, Park JW (2010) Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1α. Mol Cell 38(6):864–878PubMedCrossRefGoogle Scholar
  14. 14.
    McCay CM, Crowell MF, Maynard LA (1989) The effect of retarded growth upon the length of life span and upon the ultimate body size. J Nutr 5(3):155–171Google Scholar
  15. 15.
    Miyazaki R, Ichiki T, Hashimoto T, Inanaga K, Imayama I, Sadoshima J, Sunagawa K (2008) SIRT1, a longevity gene, downregulates angiotensin II type 1 receptor expression in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 28(7):1263–1269PubMedCrossRefGoogle Scholar
  16. 16.
    Stępień A, Izdebska M, Grzanka A (2007) The types of cell death. Postepy Hig Med Dosw 61(9):420–428Google Scholar
  17. 17.
    Yamamoto H, Schoonjans K, Auwerx J (2007) Sirtuin functions in health and disease. Mol Endocrinol 21(8):1745–1755PubMedCrossRefGoogle Scholar
  18. 18.
    Yu J, Auwerx J (2009) The role of sirtuins in the control of metabolic homeostasis integrative physiology. Ann NY Acad Sci 1173(1):E10–E19PubMedCrossRefGoogle Scholar

Copyright information

© University of Navarra 2013

Authors and Affiliations

  • Dorota Polak-Jonkisz
    • 1
  • Krystyna Laszki-Szcząchor
    • 2
  • Leopold Rehan
    • 3
  • Witold Pilecki
    • 2
  • Henryk Filipowski
    • 2
  • Małgorzata Sobieszczańska
    • 2
  1. 1.Department of Paediatric NephrologyWroclaw Medical UniversityWroclawPoland
  2. 2.Department of PathophysiologyWroclaw Medical UniversityWrocławPoland
  3. 3.Clinical Centre of Wroclaw Medical UniversityWroclawPoland

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