Cardiac Acetylation in Metabolic Diseases

Dubois‐Deruy, Emilie; Masri, Yara El El; Turkieh, Annie; Amouyel, Philippe; Pinet, Florence; Annicotte, Jean-Sébastien

doi:10.3390/biomedicines10081834

Cited by 8 publications

(4 citation statements)

References 96 publications

(168 reference statements)

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“…Allantoin is a biomarker for oxidative stress that can be triggered during hypoxia [ 82 , 83 ]. Acetylated lysine is a modified form of lysine that has been proposed to protect cells from stress damage, such as oxidative stress [ 84 , 85 , 86 ]. The role of acetylated lysine is not fully understood, however.…”

Section: Discussionmentioning

confidence: 99%

Distinct Metabolic Profiles of Ocular Hypertensives in Response to Hypoxia

Langbøl,

Rovelt,

Saruhanian

et al. 2023

IJMS

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Glaucoma is a neurodegenerative disease that affects the retinal ganglion cells (RGCs). The main risk factor is elevated intraocular pressure (IOP), but the actual cause of the disease remains unknown. Emerging evidence indicates that metabolic dysfunction plays a central role. The aim of the current study was to determine and compare the effect of universal hypoxia on the metabolomic signature in plasma samples from healthy controls (n = 10), patients with normal-tension glaucoma (NTG, n = 10), and ocular hypertension (OHT, n = 10). By subjecting humans to universal hypoxia, we aim to mimic a state in which the mitochondria in the body are universally stressed. Participants were exposed to normobaric hypoxia for two hours, followed by a 30 min recovery period in normobaric normoxia. Blood samples were collected at baseline, during hypoxia, and in recovery. Plasma samples were analyzed using a non-targeted metabolomics approach based on liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Multivariate analyses were conducted using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and univariate analysis using the Wilcoxon signed-rank test and false discovery rate (FDR) correction. Unique metabolites involved in fatty acid biosynthesis and ketone body metabolism were upregulated, while metabolites of the kynurenine pathway were downregulated in OHT patients exposed to universal hypoxia. Differential affection of metabolic pathways may explain why patients with OHT initially do not suffer or are more resilient from optic nerve degeneration. The metabolomes of NTG and OHT patients are regulated differently from control subjects and show dysregulation of metabolites important for energy production. These dysregulated processes may potentially contribute to the elevation of IOP and, ultimately, cell death of the RGCs.

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Section: Discussionmentioning

confidence: 99%

Distinct Metabolic Profiles of Ocular Hypertensives in Response to Hypoxia

Langbøl,

Rovelt,

Saruhanian

et al. 2023

IJMS

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“…Lysine acetylation is implicated in numerous cardiac disease processes, including cell metabolism, gene transcription, and enzyme activity, and is associated with metabolic disorders and heart failure. 113 Histone acetylation is involved in the regulation of smooth muscle cells (SMCs) differentiation and remodels vessels, which leads to the initiation of hypertension in individuals with metabolic syndrome. 114 Obesity-induced hyperleptinemia may lead to histone acetylation and methylation of Trpm7, thereby promoting hypertension through upregulating Trpm7 expression.…”

Section: The Dual Role Of Histone Acetylation In Vascular Diseasesmentioning

confidence: 99%

Epigenetic modifications in obesity‐associated diseases

Long,

Mao,

Liu

et al. 2024

MedComm

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The global prevalence of obesity has reached epidemic levels, significantly elevating the susceptibility to various cardiometabolic conditions and certain types of cancer. In addition to causing metabolic abnormalities such as insulin resistance (IR), elevated blood glucose and lipids, and ectopic fat deposition, obesity can also damage pancreatic islet cells, endothelial cells, and cardiomyocytes through chronic inflammation, and even promote the development of a microenvironment conducive to cancer initiation. Improper dietary habits and lack of physical exercise are important behavioral factors that increase the risk of obesity, which can affect gene expression through epigenetic modifications. Epigenetic alterations can occur in early stage of obesity, some of which are reversible, while others persist over time and lead to obesity‐related complications. Therefore, the dynamic adjustability of epigenetic modifications can be leveraged to reverse the development of obesity‐associated diseases through behavioral interventions, drugs, and bariatric surgery. This review provides a comprehensive summary of the impact of epigenetic regulation on the initiation and development of obesity‐associated cancers, type 2 diabetes, and cardiovascular diseases, establishing a theoretical basis for prevention, diagnosis, and treatment of these conditions.

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“…368 HDACs and p300/CBP mediate STAT3 acetylation to regulate gluconeogenesis. 369 The p300/CBP family and SIRT3/SIRT6 are involved in the process of obesity, [370][371][372] and the histone acetylation level is positively correlated with adipogenic differentiation. [373][374][375] p300/CBP in the PPARγ complex is the main enzyme that activates gene transcription, which can increase the expression of CEBPα and PPARγ and promote adipogenesis.…”

Section: Acetylation In Metabolic Disordersmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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Cardiac Acetylation in Metabolic Diseases

Cited by 8 publications

References 96 publications

Distinct Metabolic Profiles of Ocular Hypertensives in Response to Hypoxia

Distinct Metabolic Profiles of Ocular Hypertensives in Response to Hypoxia

Epigenetic modifications in obesity‐associated diseases

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

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