Modulatory Effect of Resveratrol on SIRT1, SIRT3, SIRT4, PGC1α and NAMPT Gene Expression Profiles in Wild-type Adult Zebrafish Liver

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2011 Jun 28

PMID 21706162

Citations 34

Authors

Helena Schirmer

Talita Carneiro Brandao Pereira

Eduardo Pacheco Rico

Denis Broock Rosemberg

Carla Denise Bonan

Mauricio Reis Bogo

Andre Arigony Souto

Affiliations

Soon will be listed here.

Abstract

Sirtuins (SIRTs) are NAD(+)-dependent deacetylases that catalyze the hydrolysis of acetyl-lysine residues. They play an important role in many physiological and pathophysiological processes, such as the regulation of lifespan and the prevention of metabolic diseases. In this study, we analyzed the effect of resveratrol on the gene expression levels of SIRT1, SIRT3, SIRT4, PGC1α, and NAMPT, as well as its effect on NAD(+) and NADH levels, in the liver of non stressed or non impaired wild-type zebrafish. Semiquantative RT-PCR assays showed that resveratrol did not change the mRNA levels of SIRT1 and PGC1α but decreased the expression levels of the SIRT3, SIRT4, and NAMPT genes. The decrease in NAMPT mRNA levels was accompanied by an increase in NADH levels, thereby decreasing the NAD(+)/H ratio. Taken together, our results suggest that resveratrol plays a modulatory role in the transcription of the NAMPT, SIRT3, and SIRT4 genes. Zebrafish is an interesting tool that can be used to understand the mechanisms of SIRTs and NAMPT metabolism and to help develop therapeutic compounds. However, further investigations using healthy experimental animals are required to study the modulation of the SIRT and NAMPT genes by resveratrol before it is used as a nutraceutical compound in healthy humans.

Citing Articles

Protective effect of oleuropein on the brain tissue in D-Galactose-induced aging in rat model.

Hu X, Zhao N, Ranjbar E, Foruozandeh H, Nahal A, Asadoola Y Mol Biol Rep. 2024; 52(1):67.

PMID: 39704928 DOI: 10.1007/s11033-024-10165-9.

Epigenetic Cross-Talk Between Sirt1 and Dnmt1 Promotes Axonal Regeneration After Spinal Cord Injury in Zebrafish.

Gupta S, Hui S Mol Neurobiol. 2024; 62(2):2396-2419.

PMID: 39110393 DOI: 10.1007/s12035-024-04408-w.

Deacetylation mimetic mutation of mitochondrial SOD2 attenuates ANG II-induced hypertension by protecting against oxidative stress and inflammation.

Dikalova A, Ao M, Tkachuk L, Dikalov S Am J Physiol Heart Circ Physiol. 2024; 327(2):H433-H443.

PMID: 38904850 PMC: 11442025. DOI: 10.1152/ajpheart.00162.2024.

The effects of combined resveratrol and high intensity interval training on the hippocampus in aged male rats: An investigation into some signaling pathways related to mitochondria.

Amirazodi M, Mehrabi A, Rajizadeh M, Bejeshk M, Esmaeilpour K, Daryanoosh F Iran J Basic Med Sci. 2022; 25(2):254-262.

PMID: 35655601 PMC: 9124540. DOI: 10.22038/IJBMS.2022.57780.12853.

Transcriptome Analysis of Juvenile Tilapia () Blood, Fed With Different Concentrations of Resveratrol.

Zheng Y, Wu W, Hu G, Qiu L, Chen J Front Physiol. 2020; 11:600730.

PMID: 33362577 PMC: 7755862. DOI: 10.3389/fphys.2020.600730.

References

Sauve A, Wolberger C, Schramm V, Boeke J . The biochemistry of sirtuins. Annu Rev Biochem. 2006; 75:435-65. DOI: 10.1146/annurev.biochem.74.082803.133500. View

Baur J . Biochemical effects of SIRT1 activators. Biochim Biophys Acta. 2009; 1804(8):1626-34. PMC: 2886178. DOI: 10.1016/j.bbapap.2009.10.025. View

Zon L, Peterson R . In vivo drug discovery in the zebrafish. Nat Rev Drug Discov. 2005; 4(1):35-44. DOI: 10.1038/nrd1606. View

Haigis M, Guarente L . Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006; 20(21):2913-21. DOI: 10.1101/gad.1467506. View

Revollo J, Korner A, Mills K, Satoh A, Wang T, Garten A . Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab. 2007; 6(5):363-75. PMC: 2098698. DOI: 10.1016/j.cmet.2007.09.003. View

de Boer J, Bahr M, Boker K, Manns M, Tietge U . Plasma levels of PBEF/Nampt/visfatin are decreased in patients with liver cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2008; 296(2):G196-201. DOI: 10.1152/ajpgi.00029.2008. View

Barbazuk W, Korf I, Kadavi C, Heyen J, Tate S, Wun E . The syntenic relationship of the zebrafish and human genomes. Genome Res. 2000; 10(9):1351-8. PMC: 310919. DOI: 10.1101/gr.144700. View

Ahn B, Kim H, Song S, Lee I, Liu J, Vassilopoulos A . A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci U S A. 2008; 105(38):14447-52. PMC: 2567183. DOI: 10.1073/pnas.0803790105. View

Nunes T, Almeida L, Rocha J, Falcao A, Fernandes-Lopes C, Loureiro A . Pharmacokinetics of trans-resveratrol following repeated administration in healthy elderly and young subjects. J Clin Pharmacol. 2009; 49(12):1477-82. DOI: 10.1177/0091270009339191. View

10.

Beher D, Wu J, Cumine S, Kim K, Lu S, Atangan L . Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des. 2009; 74(6):619-24. DOI: 10.1111/j.1747-0285.2009.00901.x. View

11.

Pereira T, Rico E, Rosemberg D, Schirmer H, Dias R, Souto A . Zebrafish as a model organism to evaluate drugs potentially able to modulate sirtuin expression. Zebrafish. 2011; 8(1):9-16. DOI: 10.1089/zeb.2010.0677. View

12.

Hirschey M, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard D . SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature. 2010; 464(7285):121-5. PMC: 2841477. DOI: 10.1038/nature08778. View

13.

Hallows W, Lee S, Denu J . Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci U S A. 2006; 103(27):10230-10235. PMC: 1480596. DOI: 10.1073/pnas.0604392103. View

14.

Imai S, Guarente L . Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases. Trends Pharmacol Sci. 2010; 31(5):212-20. PMC: 3526941. DOI: 10.1016/j.tips.2010.02.003. View

15.

Kong X, Wang R, Xue Y, Liu X, Zhang H, Chen Y . Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS One. 2010; 5(7):e11707. PMC: 2908542. DOI: 10.1371/journal.pone.0011707. View

16.

Szkudelska K, Szkudelski T . Resveratrol, obesity and diabetes. Eur J Pharmacol. 2010; 635(1-3):1-8. DOI: 10.1016/j.ejphar.2010.02.054. View

17.

Nasrin N, Wu X, Fortier E, Feng Y, Bare O, Chen S . SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells. J Biol Chem. 2010; 285(42):31995-2002. PMC: 2952200. DOI: 10.1074/jbc.M110.124164. View

18.

Hayashida S, Arimoto A, Kuramoto Y, Kozako T, Honda S, Shimeno H . Fasting promotes the expression of SIRT1, an NAD+ -dependent protein deacetylase, via activation of PPARalpha in mice. Mol Cell Biochem. 2010; 339(1-2):285-92. DOI: 10.1007/s11010-010-0391-z. View

19.

Howitz K, Bitterman K, Cohen H, Lamming D, Lavu S, Wood J . Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003; 425(6954):191-6. DOI: 10.1038/nature01960. View

20.

Oliva J, French B, Li J, Bardag-Gorce F, Fu P, French S . Sirt1 is involved in energy metabolism: the role of chronic ethanol feeding and resveratrol. Exp Mol Pathol. 2008; 85(3):155-9. PMC: 2874466. DOI: 10.1016/j.yexmp.2008.08.002. View