Butyrate-induced GPR41 Activation Inhibits Histone Acetylation and Cell Growth

Jin Wu; Zongli Zhou; Yinghe Hu; Suzhen Dong

doi:10.1016/j.jgg.2012.05.008

Volume 39 Issue 8

Aug. 2012

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Article Navigation > Journal of Genetics and Genomics > 2012 > 39(8): 375-384

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Butyrate-induced GPR41 Activation Inhibits Histone Acetylation and Cell Growth

doi: 10.1016/j.jgg.2012.05.008

Jin Wu^{b, c},
Zongli Zhou^{b, c},
Yinghe Hu^{a, b, c},
Suzhen Dong^{a, b, c}

a
Shanghai Engineering Research Center for Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, China
b
Institute of Chemical and Translational Genomics, East China Normal University, Shanghai 200062, China
c
Shanghai Institute of Brain Functional Genomics, MOE & STCSM, Key Lab of Brain Functional Genomics, East China Normal University, Shanghai 200062, China

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Corresponding author: E-mail address: dsz79@yahoo.com.cn (Suzhen Dong)
Received Date: 2011-11-08
Accepted Date: 2012-05-09
Rev Recd Date: 2012-05-06

Available Online: 2012-07-13

Publish Date: 2012-08-20

Abstract

Abstract

Butyrate has been recently identified as a natural ligand of the G-protein-coupled receptor 41 (GPR41). In addition, it is an inhibitor of histone deacetylase (HDAC). Butyrate treatment results in the hyperacetylation of histones, with resultant multiple biological effects including inhibition of proliferation, induction of cell cycle arrest, and apoptosis, in a variety of cultured mammalian cells. However, it is not clear whether GPR41 is actively involved in the above-mentioned processes. In this study, we generated a stable cell line expressing the hGPR41 receptor in order to investigate the involvement of GPR41 on butyrate-induced biochemical and physiologic processes. We found that GPR41 activation may be a compensatory mechanism to counter the increase in histone H3 acetylation levels induced by butyrate treatment. Moreover, GPR41 had an inhibitory effect on the anti-proliferative, pro-apoptotic effects of butyrate. GPR41 expression induced cell cycle arrest at the G1-stage, while its activation by butyrate can cause more cells to pass the G1 checkpoint. These results indicated that GPR41 was associated with histone acetylation and might be involved in the acetylation-related regulation of cell processes including proliferation, apoptosis, and the cell cycle.
- GPR41,
- Butyrate,
- HDAC inhibitor,
- Anti-proliferation,
- Cell cycle arrest

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References(43)

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