Shimane Journal of Medical Science
Online ISSN : 2433-2410
Print ISSN : 0386-5959
Original Article
Effects of NAD+ Synthesis Levels on Sirtuin 1 Deacetylase Activity in Mammalian Cells
Takeshi NAKAMURA Nobumasa HARAHarumi OSAGOMineyoshi HIYOSHIMikiko KOBAYASHI-MIURAMikako TSUCHIYA
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2021 Volume 38 Issue 2 Pages 59-66

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Abstract

Sirtuin 1 (SIRT1) is an evolutionarily conserved NAD+-dependent protein deacetylase. Given that the absolute cellular concentrations of NAD+ are much higher than the reported SIRT1 Km value for NAD+ (~90 μM), we hypothesized that changes in cellular NAD+ may not be a significant regulator of SIRT1 activity. To test this hypothesis, we examined the effects of boosting or inhibiting NAD+ synthesis on the acetylation of histone H4 lysine 16 and H3 lysine 9, reported targets of SIRT1. Altering cellular NAD+ concentrations from 100 to 1400 μM did not affect acetylation, whereas treatment with a class I/II histone deacetylase inhibitor elevated acetylation dramatically. Unexpectedly, neither SIRT1 inhibition nor SIRT1 knockdown increased histone acetylation. We conclude that SIRT1 may not be the primary deacetylase of the acetylated histone residues and that global acetylation levels may not always represent cellular SIRT1 activity.

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© Shimane University, Faculty of Medicine

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