ArticleCirculation research2017
Activation of γ2-AMPK Suppresses Ribosome Biogenesis and Protects Against Myocardial Ischemia/Reperfusion Injury.
Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 74 citations in OpenAlex.
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- Ubiquitin-Related Proteostatic Programs in Cycling Fibroblast-Lineage Remodeling After Myocardial Ischemic Injury: A Hypothesis Informed by Single-Cell and Spatial Transcriptomics.International journal of molecular sciences · 2026Review
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- 2-aminoethoxydiphenylborane intervenes intracellular calcium signaling and attenuates myocardial ischemia-reperfusion injury in mice through ITPR1/MCU pathway.Scientific reports · 2025Article
- Biomarkers Related to Interferon-γ Pathway in Myocardial Ischemia-Reperfusion Injury and the Potential Molecular Mechanisms.Cardiovascular toxicology · 2025Article
- The genetic association between major depressive disorder and coronary heart disease.Acta neuropsychiatrica · 2025Article
- Injectable hydrogel with miR-222-engineered extracellular vesicles ameliorates myocardial ischemic reperfusion injury via mechanotransduction.Cell reports. Medicine · 2025Article
- SF1-specific deletion of the energy sensor AMPKγ2 induces obesity.Molecular metabolism · 2025Article
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- Isoform-specific roles of AMP-activated protein kinase in cardiac physiology and pathophysiology.Frontiers in cardiovascular medicine · 2025Review
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- Fasciculoventricular accessory pathway masked extensive atrioventricular conduction system disease in a patient with PRKAG2 syndrome.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2024Article
- Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation.iScience · 2024Article
- New Perspectives on the Role and Therapeutic Potential of Melatonin in Cardiovascular Diseases.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Molecular mechanisms underlying sarcopenia in heart failure.The journal of cardiovascular aging · 2024Article
- Refeeding-associated AMPKNature aging · 2023Article
- Effects of resveratrol on tolerance to ischemia/reperfusion injury in aged male mice: Role of autophagy and apoptosis.Food science & nutrition · 2023Article
- Characterizing Adrenergic Regulation of Glucose Transporter 4-Mediated Glucose Uptake and Metabolism in the Heart.JACC. Basic to translational science · 2023Article
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9 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleAMPK (AMP-activated protein kinase) is a heterotrimeric protein that plays an important role in energy homeostasis and cardioprotection. Two isoforms of each subunit are expressed in the heart, but the isoform-specific function of AMPK remains unclear.
objectiveWe sought to determine the role of γ2-AMPK in cardiac stress response using bioengineered cell lines and mouse models containing either isoform of the γ-subunit in the heart. METHODS AND
resultsWe found that γ2 but not γ1 or γ3 subunit translocated into nucleus on AMPK activation. Nuclear accumulation of AMPK complexes containing γ2-subunit phosphorylated and inactivated RNA Pol I (polymerase I)-associated transcription factor TIF-IA at Ser-635, precluding the assembly of transcription initiation complexes for rDNA. The subsequent downregulation of pre-rRNA level led to attenuated endoplasmic reticulum (ER) stress and cell death. Deleting γ2-AMPK led to increases in pre-rRNA level, ER stress markers, and cell death during glucose deprivation, which could be rescued by inhibition of rRNA processing or ER stress. To study the function of γ2-AMPK in the heart, we generated a mouse model with cardiac-specific deletion of γ2-AMPK (cardiac knockout [cKO]). Although the total AMPK activity was unaltered in cKO hearts because of upregulation of γ1-AMPK, the lack of γ2-AMPK sensitizes the heart to myocardial ischemia/reperfusion injury. The cKO failed to suppress pre-rRNA level during ischemia/reperfusion and showed a greater infarct size. Conversely, cardiac-specific overexpression of γ2-AMPK decreased ribosome biosynthesis and ER stress during ischemia/reperfusion insult, and the infarct size was reduced.
conclusionsThe γ2-AMPK translocates into the nucleus to suppress pre-rRNA transcription and ribosome biosynthesis during stress, thus ameliorating ER stress and cell death. Increased γ2-AMPK activity is required to protect against ischemia/reperfusion injury. Our study reveals an isoform-specific function of γ2-AMPK in modulating ribosome biosynthesis, cell survival, and cardioprotection.
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