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Could succination be involved in cardiotoxicity?
* 1, 2 , 1 , 2
1  Human biology and toxicology, UMONS, Mons, Belgium
2  Biochimie métabolique et moléculaire, UMONS, Mons, Belgium
Academic Editor: Cecília Calado

Abstract:

Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality worldwide. CVDs can be caused by different conditions, including heart failure, atherosclerosis, and ischemic cardiomyopathy. The impact of CVD on patients' quality of life is significant, highlighting the urgent need for better management, including the development of new therapies that requiredeeper molecular understanding. One possible target could be SUMOylation, a post-translational modification (PTM) in which Small Ubiquitin-like Modifier (SUMO) proteins are covalently attached to lysine residues on target proteins, which has emerged as a key regulatory process in cardiovascular development and function. In certain pathological cases, the SUMOylation of proteins that are critical for cardiac function can be significantly modified. It is particularly the case for SUMO1, one of the members of the SUMO family, which is essential for regulating SERCA2a, a calcium pump that plays an essential role in cardiac muscle relaxation by regulating calcium reuptake after contraction. In this study, we investigated how succination, a PTM caused by the reaction of fumarate with cysteine residues following its accumulation in cells, impacts SUMO1 function of SUMOylating SERCA2a. Using AC16 cardiomyocytes treated with sodium fumaric acid, we detected some metabolic shifts following the elevation of fumarate concentration via 1H-NMR spectroscopy. Moreover, Western blot analysis suggests that succinated SUMO1 has a lower capacity to SUMOylate SERCA2a. This finding indicates that succination could potentially impair calcium fluxes, thus contributing to cardiotoxic effects. By exploring the link between PTMS, succination, and SUMOylation, this research reveals a novel regulatory mechanism in cardiac physiopathology, offering potential new avenues for therapeutic intervention in cardiovascular diseases.

Keywords: Succination, SUMOyaltion, Cardiotoxicity, PTM, Calcium
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