Profiling the Murine SUMO Proteome in Response to Cardiac Ischemia and Reperfusion Injury

Molecules

Thomas Braun¹  Marion Wiesnet¹  Georg Tascher²  Luca Mendler²  PaulW. Hotz²  Stefan Müller² 

[1] Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany;Institute of Biochemistry II, Goethe University Medical School, University Hospital Building 75, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany;

关键词: cardiac I/R injury;    SUMO;    SENP;    immunoprecipitation;    mass spectrometry;    proteomics;   

DOI  :  10.3390/molecules25235571

来源: DOAJ

【 摘 要 】

SUMOylation is a reversible posttranslational modification pathway catalyzing the conjugation of small ubiquitin-related modifier (SUMO) proteins to lysine residues of distinct target proteins. SUMOylation modifies a wide variety of cellular regulators thereby affecting a multitude of key processes in a highly dynamic manner. The SUMOylation pathway displays a hallmark in cellular stress-adaption, such as heat or redox stress. It has been proposed that enhanced cellular SUMOylation protects the brain during ischemia, however, little is known about the specific regulation of the SUMO system and the potential target proteins during cardiac ischemia and reperfusion injury (I/R). By applying left anterior descending (LAD) coronary artery ligation and reperfusion in mice, we detect dynamic changes in the overall cellular SUMOylation pattern correlating with decreased SUMO deconjugase activity during I/R injury. Further, unbiased system-wide quantitative SUMO-proteomics identified a sub-group of SUMO targets exhibiting significant alterations in response to cardiac I/R. Notably, transcription factors that control hypoxia- and angiogenesis-related gene expression programs, exhibit altered SUMOylation during ischemic stress adaptation. Moreover, several components of the ubiquitin proteasome system undergo dynamic changes in SUMO conjugation during cardiac I/R suggesting an involvement of SUMO signaling in protein quality control and proteostasis in the ischemic heart. Altogether, our study reveals regulated candidate SUMO target proteins in the mouse heart, which might be important in coping with hypoxic/proteotoxic stress during cardiac I/R injury.

【 授权许可】

Unknown