ACE2 (angiotensin-converting enzyme 2) counterbalances the actions of ACE (angiotensin-converting enzyme) by metabolizing its catalytic product, the vasoactive and fibrogenic peptide AngII (angiotensin II), into Ang-(1–7) [angiotensin-(1–7)]. Enhanced ACE2 expression may be protective in diabetes, cardiovascular disease and cancer. However, relatively little is known about the specific physiological factors regulating ACE2 expression. In the present paper, we show, by Western blotting and qPCR (quantitative real-time PCR), that ACE2 expression is increased under conditions of cell stress, including hypoxic conditions, IL (interleukin)-1β treatment and treatment with the AMP mimic AICAR (5-amino-4-imidazolecarboxamide riboside). The NAD+-dependent deacetylase SIRT1 (silent information regulator T1) was found to be up-regulated after AICAR treatment but, conversely, was down-regulated after IL-1β treatment. ChIP analysis demonstrated that SIRT1 bound to the ACE2 promoter and that binding was increased after AICAR treatment, but decreased after IL-1β treatment. Inhibition of SIRT1 activity ablated the AICAR-induced increase in ACE2. In conclusion, we have established that the expression of the ACE2 transcript is controlled by the activity of SIRT1 under conditions of energy stress.
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Research Article|
December 11 2013
Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress
Nicola E. Clarke;
Nicola E. Clarke
*School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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Nikolai D. Belyaev;
Nikolai D. Belyaev
*School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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Daniel W. Lambert;
Daniel W. Lambert
†Integrated Biosciences, School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, U.K.
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Anthony J. Turner
*School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
Correspondence: Professor Anthony J. Turner (email [email protected]).
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Publisher: Portland Press Ltd
Received:
July 19 2013
Revision Received:
October 09 2013
Accepted:
October 23 2013
Accepted Manuscript online:
October 23 2013
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 126 (7): 507–516.
Article history
Received:
July 19 2013
Revision Received:
October 09 2013
Accepted:
October 23 2013
Accepted Manuscript online:
October 23 2013
Citation
Nicola E. Clarke, Nikolai D. Belyaev, Daniel W. Lambert, Anthony J. Turner; Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress. Clin Sci (Lond) 1 April 2014; 126 (7): 507–516. doi: https://doi.org/10.1042/CS20130291
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