A subset of 26S proteasomes is activated at critically low ATP concentrations and contributes to myocardial injury during cold ischemia.

Biochemical and Biophysical Research Communications
Qing GengMatthias Majetschak

Abstract

Molecular mechanisms leading to myocardial injury during warm or cold ischemia are insufficiently understood. Although proteasomes are thought to contribute to myocardial ischemia-reperfusion injury, their roles during the ischemic period remain elusive. Because donor hearts are commonly exposed to prolonged global cold ischemia prior to cardiac transplantation, we evaluated the role and regulation of the proteasome during cold ischemic storage of rat hearts in context of the myocardial ATP content. When measured at the actual tissue ATP concentration, cardiac proteasome peptidase activity increased by 225% as ATP declined during cold ischemic storage of hearts in University of Wisconsin (UW) solution for up to 48h. Addition of the specific proteasome inhibitor epoxomicin to the UW solution inhibited proteasome activity in the cardiac extracts, significantly reduced edema formation and preserved the ultrastructural integrity of the cardiomyocyte. Utilizing purified 20S/26S proteasome enzyme preparations, we demonstrate that this activation can be attributed to a subset of 26S proteasomes which are stable at ATP concentrations far below physiological levels, that ATP negatively regulates its activity and that maximal activation ...Continue Reading

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Citations

Sep 2, 2010·Cell Research·Hongbiao HuangJinbao Liu
May 25, 2012·Critical Care Medicine·Todd A BakerMatthias Majetschak
Dec 12, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Justine Calise, Saul R Powell
May 29, 2012·Molecular Medicine·Harold H BachMatthias Majetschak
Oct 16, 2013·Expert Opinion on Investigational Drugs·Apostolos N KandilisStamatios Theocharis
Oct 16, 2015·European Journal of Immunology·Sebastián A RiquelmeAlexis M Kalergis
Apr 6, 2012·Experimental and Molecular Pathology·Susagna Padrissa-AltésJoan Roselló-Catafau
May 16, 2012·Biochimie·Emanuele S ScarpaTiziana Cacciamani
Sep 30, 2010·Biochemical and Biophysical Research Communications·Todd A BakerMatthias Majetschak
Sep 16, 2010·Biochimica Et Biophysica Acta·Yi-Fan Li, Xuejun Wang
Apr 17, 2015·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Tian-Shu LiuQing Geng
May 28, 2016·International Journal of Molecular Sciences·Emma Folch-PuyJoan Roselló-Catafau
Nov 1, 2017·International Journal of Molecular Sciences·Arnau Panisello-RosellóJoan Roselló-Catafau
Jun 1, 2014·Journal of Burn Care & Research : Official Publication of the American Burn Association·Yee M WongMatthias Majetschak
Jul 24, 2015·Journal of Burn Care & Research : Official Publication of the American Burn Association·P Geoff VanaMatthias Majetschak
Apr 28, 2018·Clinical and Experimental Pharmacology & Physiology·Sean P NassoiyMatthias Majetschak
Oct 12, 2018·American Journal of Physiology. Renal Physiology·Sorena LoNirmala Parajuli
Apr 8, 2014·CNS Neuroscience & Therapeutics·Gabriella MifsudMario Valentino
Jan 29, 2013·The Journal of Trauma and Acute Care Surgery·Harold H BachMatthias Majetschak
Apr 28, 2017·Open Biology·Piotr BragoszewskiAgnieszka Chacinska
Aug 23, 2018·World Journal of Gastroenterology : WJG·Norma AlvaTeresa Carbonell
Jan 17, 2015·World Journal of Gastroenterology : WJG·Mohamed BejaouiJoan Roselló-Catafau
May 21, 2020·International Journal of Molecular Sciences·Sorena B LoNirmala Parajuli
May 28, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Matthias Majetschak
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Dec 10, 2020·Polymers·Lucia Račková, Erika Csekes
May 7, 2020·Metabolism: Clinical and Experimental·Patrick R DavisJeffrey J Brault

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