ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Gestational Leucylation Suppresses Embryonic T-Box Transcription Factor 5 Signal and Causes Congenital Heart Disease.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 58 citations in OpenAlex.
- Mechanistic and functional integration of sirtuin deacylases: from substrate specificity to biological outcomes.Glycoconjugate journal · 2026Review
- ELABELA Targets Mitochondria to Modulate Heart Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sirtuin 3 in diabetic kidney disease: mechanisms and pharmacotherapy.Renal failure · 2025Review
- Analyzing exosomal miRNA profiles in tetralogy of fallot fetuses' amniotic fluid.Scientific reports · 2025Article
- NOTCH1 mitochondria localization during heart development promotes mitochondrial metabolism and the endothelial-to-mesenchymal transition in mice.Nature communications · 2024Article
- High gestational leucine level dampens WDPCP/MAPK signaling to impair the EMT and migration of cardiac microvascular endothelial cells in congenital heart defects.Pulmonary circulation · 2024Article
- Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Identification of Key Factors in Cartilage Tissue During the Progression of Osteoarthritis Using a Non-targeted Metabolomics Strategy.Phenomics (Cham, Switzerland) · 2024Article
- m6A epitranscriptomic and epigenetic crosstalk in cardiac fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Branched-chain amino acids deficiency promotes diabetic cardiomyopathy by activating autophagy of cardiac fibroblasts.Theranostics · 2024Article
- Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease.EMBO molecular medicine · 2023Article
- Genetic Alterations of Transcription Factors and Signaling Molecules Involved in the Development of Congenital Heart Defects-A Narrative Review.Children (Basel, Switzerland) · 2023Review
- Role of Sirtuin 3 in Degenerative Diseases of the Central Nervous System.Biomolecules · 2023Review
- Boron nitride nanocage as drug delivery systems for chloroquine, as an effective drug for treatment of coronavirus disease: A DFT study.Inorganic chemistry communications · 2023Article
- Formate Might Be a Novel Potential Serum Metabolic Biomarker for Type 2 Diabetic Peripheral Neuropathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
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- Influence of the coiling porosity on the risk reduction of the cerebral aneurysm rupture: computational study.Scientific reports · 2022Article
- In-Vitro, In-Vivo, Molecular Docking and ADMET Studies of 2-Substituted 3,7-Dihydroxy-4H-chromen-4-one for Oxidative Stress, Inflammation and Alzheimer's Disease.Metabolites · 2022Article
- Integrated Bioinformatics-Based Subtractive Genomics Approach to Decipher the Therapeutic Drug Target and Its Possible Intervention against Brucellosis.Bioengineering (Basel, Switzerland) · 2022Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Dysregulated maternal nutrition, such as vitamin deficiencies and excessive levels of glucose and fatty acids, increases the risk for congenital heart disease (CHD) in the offspring. However, the association between maternal amino-acid levels and CHD is unclear. Here, it is shown that increased leucine levels in maternal plasma during the first trimester are associated with elevated CHD risk in the offspring. High levels of maternal leucine increase embryonic lysine-leucylation (K-Leu), which is catalyzed by leucyl-tRNA synthetase (LARS). LARS preferentially binds to and catalyzes K-Leu modification of lysine 339 within T-box transcription factor TBX5, whereas SIRT3 removes K-Leu from TBX5. Reversible leucylation retains TBX5 in the cytoplasm and inhibits its transcriptional activity. Increasing embryonic K-Leu levels in high-leucine-diet fed or Sirt3 knockout mice causes CHD in the offspring. Targeting K-Leu using the leucine analogue leucinol can inhibit LARS activity, reverse TBX5 K-Leu modification, and decrease the occurrence of CHD in high-leucine-diet fed mice. This study reveals that increased maternal leucine levels increases CHD risk in the offspring through inhibition of embryonic TBX5 signaling, indicating that leucylation exerts teratogenic effects during heart development and may be an intervening target of CHD.
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