Sirtuin 6 (SIRT6) Activity Assays

Rahnasto-Rilla, Minna; Lahtela‐Kakkonen, Maija; Moaddel, Ruin

doi:10.1007/978-1-4939-3667-0_17

Cited by 7 publications

(5 citation statements)

References 17 publications

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“…A set of flavonoids (Fig. 1B ; Table S1 ) and phenolic acids (Table S2 ) were tested using recently developed HPLC-based SIRT6 assay 14 , 19 , 20 with two substrate concentrations by determining the level of deacetylated peptide H3K9. SIRT6 activity was determined at multiple concentrations of the tested compounds (Fig.…”

Section: Resultsmentioning

confidence: 99%

Natural polyphenols as sirtuin 6 modulators

Rahnasto-Rilla

Tyni

Huovinen

et al. 2018

Sci Rep

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118

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Flavonoids are polyphenolic secondary metabolites synthesized by plants and fungus with various pharmacological effects. Due to their plethora of biological activities, they have been studied extensively in drug development. They have been shown to modulate the activity of a NAD+-dependent histone deacetylase, SIRT6. Because SIRT6 has been implicated in longevity, metabolism, DNA-repair, and inflammatory response reduction, it is an interesting target in inflammatory and metabolic diseases as well as in cancer. Here we show, that flavonoids can alter SIRT6 activity in a structure dependent manner. Catechin derivatives with galloyl moiety displayed significant inhibition potency against SIRT6 at 10 µM concentration. The most potent SIRT6 activator, cyanidin, belonged to anthocyanidins, and produced a 55-fold increase in SIRT6 activity compared to the 3–10 fold increase for the others. Cyanidin also significantly increased SIRT6 expression in Caco-2 cells. Results from the docking studies indicated possible binding sites for the inhibitors and activators. Inhibitors likely bind in a manner that could disturb NAD+ binding. The putative activator binding site was found next to a loop near the acetylated peptide substrate binding site. In some cases, the activators changed the conformation of this loop suggesting that it may play a role in SIRT6 activation.

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Section: Resultsmentioning

confidence: 99%

Natural polyphenols as sirtuin 6 modulators

Rahnasto-Rilla

Tyni

Huovinen

et al. 2018

Sci Rep

Self Cite

118

100

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show abstract

“…In this study, we used a previously developed HPLC deacetylation assay that estimates SIRT6 activity by measuring changes in the level of deacetylated peptide H3K9, over the substrate (H3K9Ac) [ 13 , 20 ], to determine SIRT6 activity in complex matrices. Five species of brown algae were tested for SIRT6 modulating activity at two concentrations ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

The Identification of a SIRT6 Activator from Brown Algae Fucus distichus

et al. 2017

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Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity, although in most cases their mechanisms of action are not understood. In this study, extracts generated from five brown algae (Fucus dichitus, Fucus vesiculosus (Linnaeus), Cytoseira tamariscofolia, Cytoseira nodacaulis, Alaria esculenta) were tested for their ability to activate SIRT6 resulting in H3K9 deacetylation. Three of the five macroalgal extracts caused a significant increase of H3K9 deacetylation, and the effect was most pronounced for F. dichitus. The compound responsible for this in vitro activity was identified by mass spectrometry as fucoidan.

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“…Third, the galloyl moiety linked to hydroxyl extends the molecule to a deeper area toward V154 residues likely to enhance the inhibitory activity 300,310 . Among them, CG (compound 12 ) and gallocatechin gallate (compound 13 ) are the most potent analogues with an IC 50 value of 2.5 and 5.4 µM, respectively, in the HPLC‐based SIRT6 deacetylation assays 310,313 . In addition, CG was detected to successfully increase the H3K56 acetylation at 25 µM in SIRT6‐WT human U2OS cells, but not in SIRT6‐KO cells 300 …”

Section: Sirt6 Modulatorsmentioning

confidence: 99%

Emerging roles of SIRT6 in human diseases and its modulators

Liu

Chen

Liu

et al. 2020

Medicinal Research Reviews

103

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The biological functions of sirtuin 6 (SIRT6; e.g., deacetylation, defatty‐acylation, and mono‐ADP‐ribosylation) play a pivotal role in regulating lifespan and several fundamental processes controlling aging such as DNA repair, gene expression, and telomeric maintenance. Over the past decades, the aberration of SIRT6 has been extensively observed in diverse life‐threatening human diseases. In this comprehensive review, we summarize the critical roles of SIRT6 in the onset and progression of human diseases including cancer, inflammation, diabetes, steatohepatitis, arthritis, cardiovascular diseases, neurodegenerative diseases, viral infections, renal and corneal injuries, as well as the elucidation of the related signaling pathways. Moreover, we discuss the advances in the development of small molecule SIRT6 modulators including activators and inhibitors as well as their pharmacological profiles toward potential therapeutics for SIRT6‐mediated diseases.

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Sirtuin 6 (SIRT6) Activity Assays

Cited by 7 publications

References 17 publications

Natural polyphenols as sirtuin 6 modulators

Natural polyphenols as sirtuin 6 modulators

The Identification of a SIRT6 Activator from Brown Algae Fucus distichus

Emerging roles of SIRT6 in human diseases and its modulators

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