Identification of Malonylation, Succinylation, and Glutarylation in Serum Proteins of Acute Myocardial Infarction Patients

Zhou, Jie; Du, Yipeng; Xue, Yan; Miao, Guobin; Wei, Taotao; Zhang, Ping

doi:10.1002/prca.201900103

Cited by 16 publications

(25 citation statements)

References 25 publications

(29 reference statements)

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“…By contrast, inhibition of MCD leads to increasing myocardial levels of malonyl-CoA, an intracellular inhibitor of mitochondrial FA uptake, to decrease FA oxidation and enhance glucose oxidation, which ultimately causes the decrease in toxic byproducts (lactate and protons) to augment cardiac function and cardiac efficiency and prevents myocardial ischemic injury [109][110][111]. Also, a recent study reveals the malonylation of serum proteins in acute MI humans and rats [112]. Therefore, MCD is an essential regulator of protein malonylation and CVDs.…”

Section: Malonate and Malonylationmentioning

confidence: 99%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Metabolic dysfunction is a fundamental core mechanism underlying CVDs. Previous studies generally focused on the roles of long-chain fatty acids (LCFAs) in CVDs. However, a growing body of study has implied that short-chain fatty acids (SCFAs: namely propionate, malonate, butyrate, 2-hydroxyisobutyrate (2-HIBA), β-hydroxybutyrate, crotonate, succinate, and glutarate) and their cognate acylations (propionylation, malonylation, butyrylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, crotonylation, succinylation, and glutarylation) participate in CVDs. Here, we attempt to provide an overview landscape of the metabolic pattern of SCFAs in CVDs. Especially, we would focus on the SCFAs and newly identified acylations and their roles in CVDs, including atherosclerosis, hypertension, and heart failure. Clinical Science (2020) 134 657-676 https://doi.org/10.1042/CS20200128 cofactors in certain protein acylations, such as propionylation [14], malonylation [15], butyrylation [14], 2-hydroxyisobutyrylation [16], β-hydroxybutyrylation [17], crotonylation [18], succinylation [19], and glutarylation [20]. These discoveries give us a deeper understanding of PTM. Among PTMs, protein acetylation is the earliest discovered and most studied. Similar to protein acetylation, various studies have shown that these newly discovered PTMs are also involved in physiological and pathophysiological processes, including cardiovascular homeostasis.Here in this review, we will summarize SCFAs, protein acylations, and their emerging roles in CVDs, including atherosclerosis, hypertension, and heart failure. The metabolic pattern and FAs in CVDsThe heart is an 'omnivore' , using FAs, glucose, lactate, ketone bodies, and amino acids as metabolic substrates [5,6]. The substrates utilized by the embryonic heart are significantly different from those used by the adult heart. The embryonic heart depends primarily on glycolysis as well as lactate oxidation to produce energy [21]. The newborn and adult heart shift toward the remarkable utilization of FAs to meet cardiac energy demand [5,9]. In failing hearts, a decrease in FA oxidation and an increase in glycolysis are critically involved in cardiac dysfunction [22]. As thus, the metabolic pattern is essential for maintaining cardiac and vascular functions.Diabetes, hypertension, and obesity contribute to heart failure syndrome. Accumulating evidence suggests that hypertension, ischemic hearts, and heart failure induce a shift in substrate toward the remarkable utilization of glucose to generate energy. Despite this shift, the FA oxidation remains to make much energy for the diseased heart [23]. Since FAs are the predominant substrates for cardiomyocytes, alterations in FA metabolism have been implicated as causal in cardiac diseases. FAs within cells and in the circulation are critically involved in cardiometabolic diseases. CVDs are closely associated with lifestyle and metabolic status, which affect circul...

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Section: Malonate and Malonylationmentioning

confidence: 99%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

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“… Bao et al (2019) revealed that Kglu occurs at 27 lysine residues on human core histones. Zhou et al (2020) reported 4 kinds of glutarylated proteins with 10 sites in human serum. It shows that Kglu occurred in different species, and most of glutarylated proteins contain at least two Kglu sites in Table 1 .…”

Section: Proteomic Profiling Of Lysine Glutarylationmentioning

confidence: 99%

“…Antibodies are crucial for experimental studies, especially for the identification of protein PTMs. Therefore, we have reviewed the experimental studies on antibody for lysine glutarylation, and found eight related articles ( Tan et al, 2014 ; Xie L. et al, 2016 ; Zhou et al, 2016 , 2020 ; Schmiesing et al, 2018 ; Bao et al, 2019 ; Cheng et al, 2019 ; Wang et al, 2020 ). The specific Methods and reagents used in previous studies were summarized in Supplementary Table 1 .…”

Section: Proteomic Profiling Of Lysine Glutarylationmentioning

confidence: 99%

“…For the remaining three studies, Bao et al (2019) raised a rabbit polyclonal antibody which is site specific against histones glutarylation and conducted dot-blot and western blot analysis to verify whether the antibody has high specificity. Although the origin of the antibodies was not specified in the remaining two papers, western blot analysis or mass spectrometer were also performed to verify the specificity of antibodies ( Wang et al, 2020 ; Zhou et al, 2020 ).…”

Section: Proteomic Profiling Of Lysine Glutarylationmentioning

confidence: 99%

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Functions and Mechanisms of Lysine Glutarylation in Eukaryotes

Xie

Xiao

Meng

et al. 2021

Front. Cell Dev. Biol.

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Lysine glutarylation (Kglu) is a newly discovered post-translational modification (PTM), which is considered to be reversible, dynamic, and conserved in prokaryotes and eukaryotes. Recent developments in the identification of Kglu by mass spectrometry have shown that Kglu is mainly involved in the regulation of metabolism, oxidative damage, chromatin dynamics and is associated with various diseases. In this review, we firstly summarize the development history of glutarylation, the biochemical processes of glutarylation and deglutarylation. Then we focus on the pathophysiological functions such as glutaric acidemia 1, asthenospermia, etc. Finally, the current computational tools for predicting glutarylation sites are discussed. These emerging findings point to new functions for lysine glutarylation and related enzymes, and also highlight the mechanisms by which glutarylation regulates diverse cellular processes.

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“…glycolysis and the synthesis of bioactive substances. Malonylation has been reported to use malonyl-CoA as a substrate in the reaction [9]. At present, with advances in high-throughput experimental techniques, thousands of peptide segments containing lysine malonylation have been discovered.…”

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confidence: 99%

Systematic Analysis of the Lysine Malonylome in Sanghuangporus Sanghuang

Wang

Zhang

et al. 2020

Preprint

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Background: Sanghuangporus sanghuang is a well-known traditional medicinal mushroom associated with mulberry, which has enormous economic and medical value. Despite being known for many years, proteomics studies of S. sanghuang have not been reported. In this paper, a series of technologies, such as high-performance liquid chromatography (HPLC) classification technology, malonyl peptide segment enrichment technology and proteomics technology, are combined to study the qualitative analysis of malonylation in S. sanghuang.Results: Strategies for qualitative proteomics included malonyl enrichment and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). In total, 714 malonyl modification sites were matched to 255 different proteins. The analysis indicated that malonyl modifications are involved in a wide range of acellular functions and displayed a distinct subcellular localization.Bioinformatics analysis indicates that malonylated proteins are engaged in different metabolic pathways, including glyoxylate and dicarboxylate metabolism, glycolysis/gluconeogenesis, and the tricarboxylic acid (TCA) cycle; consequently, a total of 26 enzymes related to triterpene and polysaccharide biosynthesis were found to be malonylated.Conclusions: These findings suggest that malonylation is associated with many metabolic pathways, particularly the metabolism of bioactive compounds. This paper provides the first comprehensive survey of malonylation in S. sanghuang.

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Identification of Malonylation, Succinylation, and Glutarylation in Serum Proteins of Acute Myocardial Infarction Patients

Cited by 16 publications

References 25 publications

Short-chain fatty acid, acylation and cardiovascular diseases

Short-chain fatty acid, acylation and cardiovascular diseases

Functions and Mechanisms of Lysine Glutarylation in Eukaryotes

Systematic Analysis of the Lysine Malonylome in Sanghuangporus Sanghuang

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