Role of SIRT1 in Modulating Acetylation of the Sarco-Endoplasmic Reticulum Ca2+-ATPase in Heart Failure.

Circulation Research
Przemek A GorskiChangwon Kho

Abstract

SERCA2a, sarco-endoplasmic reticulum Ca2+-ATPase, is a critical determinant of cardiac function. Reduced level and activity of SERCA2a are major features of heart failure. Accordingly, intensive efforts have been made to develop efficient modalities for SERCA2a activation. We showed that the activity of SERCA2a is enhanced by post-translational modification with SUMO1 (small ubiquitin-like modifier 1). However, the roles of other post-translational modifications on SERCA2a are still unknown. In this study, we aim to assess the role of lysine acetylation on SERCA2a function and determine whether inhibition of lysine acetylation can improve cardiac function in the setting of heart failure. The acetylation of SERCA2a was significantly increased in failing hearts of humans, mice, and pigs, which is associated with the reduced level of SIRT1 (sirtuin 1), a class III histone deacetylase. Downregulation of SIRT1 increased the SERCA2a acetylation, which in turn led to SERCA2a dysfunction and cardiac defects at baseline. In contrast, pharmacological activation of SIRT1 reduced the SERCA2a acetylation, which was accompanied by recovery of SERCA2a function and cardiac defects in failing hearts. Lysine 492 (K492) was of critical importance...Continue Reading

References

Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·M I MiyamotoR J Hajjar
Oct 18, 2000·Free Radical Biology & Medicine·A K Jaiswal
Mar 21, 2002·Nature Reviews. Cancer·P MarksW K Kelly
Apr 19, 2002·The Journal of Biological Chemistry·Gregory DavidRonald A DePinho
Apr 30, 2003·Molecular Cell·David GirdwoodRonald T Hay
May 2, 2003·Molecular and Cellular Biology·Tetsuhiko YanazumeToru Kita
Oct 28, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yuzuru Shiio, Robert N Eisenman
Mar 4, 2005·Molecular and Cellular Biology·Serge Grégoire, Xiang-Jiao Yang
Dec 20, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Heon Joo ParkChang W Song
Jan 16, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Susumu SakataRoger J Hajjar
Apr 21, 2007·Circulation Research·Ralph R AlcendorJunichi Sadoshima
Jul 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Erik A BeyDavid A Boothman
Feb 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·In Hye LeeToren Finkel
Mar 18, 2008·Journal of the American College of Cardiology·Yoshiaki KawaseRoger J Hajjar
Jul 31, 2008·Nature Clinical Practice. Cardiovascular Medicine·Yoshiaki Kawase, Roger J Hajjar
Aug 14, 2008·Circulation·Jian Qin WeiNanette H Bishopric
Mar 31, 2009·Journal of Cardiac Failure·Brian E JaskiUNKNOWN Calcium Up-Regulation by Percutaneous Administration of Gene Therapy In Cardiac Disease (CUPID) Trial Investigators
Jan 19, 2010·Annual Review of Pathology·Marcia C Haigis, David A Sinclair
Nov 10, 2010·Circulation·Chiao-Po HsuJunichi Sadoshima
Mar 26, 2011·Journal of Aging Research·Gregory R Wagner, R Mark Payne
Jun 29, 2011·Circulation·Mariell JessupUNKNOWN Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) Investigators
Sep 9, 2011·Nature·Changwon KhoRoger J Hajjar
May 25, 2012·Basic Research in Cardiology·Masaya TannoTetsuji Miura
Oct 24, 2012·Nature Reviews. Cardiology·Changwon KhoRoger J Hajjar
Jul 12, 2013·PloS One·D Brian FosterBrian O'Rourke
Nov 15, 2013·Science Translational Medicine·Lisa TilemannRoger J Hajjar
Dec 25, 2013·Molecular Systems Biology·Pedro BeltraoVera van Noort
Feb 11, 2014·Neuron·A Zara Herskovits, Leonard Guarente
Jun 4, 2014·Antioxidants & Redox Signaling·Ahyoung LeeChangwon Kho
Jun 13, 2015·Nature Communications·Changwon KhoRoger J Hajjar
Jun 27, 2015·European Heart Journal·Stephan WinnikChristian M Matter

❮ Previous
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Citations

May 17, 2019·International Journal of Molecular Sciences·Shanna Hamilton, Dmitry Terentyev
Jul 3, 2019·Cell Death & Disease·Bitna LimYong-Keun Jung
Apr 29, 2020·Journal of Cellular and Molecular Medicine·Hsiang-Yu YangChih-Yuan Lin
Oct 6, 2020·Frontiers in Physiology·Alexandra NjegicElizabeth J Cartwright
Jul 23, 2020·Biophysics Reviews·Amanda L DennissNicole A Beard
Apr 26, 2019·Circulation Research·Xiongwen ChenJonathan Soboloff
Nov 9, 2019·Heart Failure Reviews·Liu ZhihaoFan Guanwei
Oct 28, 2019·Frontiers in Genetics·Carolina Soler-BotijaAntoni Bayés-Genís
Jan 4, 2021·Cellular and Molecular Life Sciences : CMLS·Sanjeev Kumar SoniRussel J Reiter
Jan 6, 2021·Pflügers Archiv : European journal of physiology·Satadru K LahiriXander H T Wehrens
Feb 12, 2021·Science Translational Medicine·Mahmoud AbdellatifSimon Sedej
Nov 5, 2020·Cells·Ankush BorlepawarAshraf Yusuf Rangrez
Feb 18, 2021·Scientific Reports·Maria Carmen Asensio-LopezAntonio Lax
Apr 4, 2021·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Anderson Apolonio Silva PedrozaClaudia J Lagranha
Jul 31, 2021·Biochemical and Biophysical Research Communications·Dongfang WangGuohua Cheng
Aug 25, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Zhihao LiuGuanwei Fan
May 6, 2021·Physiological Reviews·Jun RenYingmei Zhang
Nov 30, 2021·Circulation·Mahmoud AbdellatifGuido Kroemer

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