Negative Regulation of STAT3-mediated Cellular Respiration by SirT1

Published

June 7, 2011

Author(s)

Lili Wang, Hua-Jun He, Michel Bernier, Rajib K. Paul, Alejandro Martin-Montalvo, Morten Scheibye-Knudsen, Shaoming Song, Sean M. Armour, Vilhelm A. Bohr, Yaping Zong, David A. Sinclair, Rafael de Cabo

Abstract

In mammals, the transcriptional activity of signal transducer and activator of transcription 3 (STAT3) is regulated by the deacetylase SirT1. However, whether the newly described non-genomic actions of STAT3 toward mitochondrial oxidative phosphorylation are dependent on SirT1 is unclear. In this study, SirT1 gene knockout MEF cells were used to delineate the role of SirT1 in the regulation of STAT3 mitochondrial function. Two independent approaches, including ectopic expression of SirT1 and siRNA-mediated knockdown of STAT3, led to reduction in intracellular ATP levels and increased lactate production in SirT1-KO cells that were approaching those of wild-type controls. Comparison of profiles of phospho-antibody array data indicated that the deletion of SirT1 was accompanied by constitutive activation of the pro-inflammatory NF-κB pathway, which is key for STAT3 induction and increased cellular respiration in SirT1-KO cells. These results have implications for understanding the interplay between STAT3 and SirT1 in pro-inflammatory conditions.

Citation

Journal of Biological Chemistry

Pub Type

Journals

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Keywords

Signal transducer and activator of transcription 3 (STAT3), Silent information regulator, sirtuin (SirT1), Murine embryonic fibroblasts (MEF), SirT1 gene knockout cells (SirT1-KO), Mitochondrial biogenesis and respiration, Phospho-antibody array, nuclear factor kB (NF-kB) pathway

Citation

Wang, L. , He, H. , , M. , Paul, R. , Martin-Montalvo, A. , , M. , Song, S. , Armour, S. , Bohr, V. , Zong, Y. , Sinclair, D. and de, R. (2011), Negative Regulation of STAT3-mediated Cellular Respiration by SirT1, Journal of Biological Chemistry, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=907629 (Accessed November 23, 2024)