Profiling the murine SUMO proteome in response to cardiac ischemia and reperfusion injury
- 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.
Author: | Paul W. HotzORCiD, Marion Wiesnet, Georg TascherORCiDGND, Thomas BraunORCiDGND, Stefan MüllerORCiD, Luca Mendler |
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URN: | urn:nbn:de:hebis:30:3-575515 |
DOI: | https://doi.org/10.3390/molecules25235571 |
ISSN: | 1420-3049 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/33260959 |
Parent Title (English): | Molecules |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2020/11/27 |
Date of first Publication: | 2020/11/27 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2020/12/21 |
Tag: | SENP; SUMO; cardiac I/R injury; immunoprecipitation; mass spectrometry; proteomics |
Volume: | 25 |
Issue: | Article 5571 |
Page Number: | 18 |
HeBIS-PPN: | 477814182 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |