ArticleInternational journal of cardiology2018
AMP-activated protein kinase protects against necroptosis via regulation of Keap1-PGAM5 complex.
Article in International journal of cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- AMPK as a central regulator of necroptosis: mechanistic insights and therapeutic implications.Journal of physiology and biochemistry · 2026Review
- Interaction between p-AMPK and RIPK3 reveals a mechanism by which AdipoAI suppresses necroptosis to attenuate periodontitis.Journal of translational medicine · 2026Article
- Targeting necroptosis: how does exercise protect against metabolic dysfunction-associated fatty liver disease?Frontiers in physiology · 2026Review
- Myocardial Ischemia/Reperfusion Injury: Molecular Insights, Forensic Perspectives, and Therapeutic Horizons.Cells · 2025Review
- Review
- The dual role of PGAM5 in inflammation.Experimental & molecular medicine · 2025Review
- Identification and validation of protein biomarkers for predicting gastrointestinal stromal tumor recurrence.Computational and structural biotechnology journal · 2024Article
- Ponicidin Promotes Hepatocellular Carcinoma Mitochondrial Apoptosis by Stabilizing Keap1-PGAM5 Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Nrf2 modulates the benefits of evening exercise in type 2 diabetes.Sports medicine and health science · 2023Review
- Deletion of PGAM5 Downregulates FABP1 and Attenuates Long-Chain Fatty Acid Uptake in Hepatocellular Carcinoma.Cancers · 2023Article
- The Interplay Between Autophagy and Regulated Necrosis.Antioxidants & redox signaling · 2023Review
- Muscle fiber necroptosis in pathophysiology of idiopathic inflammatory myopathies and its potential as target of novel treatment strategy.Frontiers in immunology · 2023Review
- The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury.Apoptosis : an international journal on programmed cell death · 2022Review
- Protective effects of metformin in various cardiovascular diseases: Clinical evidence and AMPK-dependent mechanisms.Journal of cellular and molecular medicine · 2022Review
- Amelioration of inflammatory myopathies by glucagon-like peptide-1 receptor agonist via suppressing muscle fibre necroptosis.Journal of cachexia, sarcopenia and muscle · 2022Article
- Discovery and repurposing of artemisinin.Frontiers of medicine · 2022Review
- Role of AMPK in Myocardial Ischemia-Reperfusion Injury-Induced Cell Death in the Presence and Absence of Diabetes.Oxidative medicine and cellular longevity · 2022Review
- PGAM5: A necroptosis gene associated with poor tumor prognosis that promotes cutaneous melanoma progression.Frontiers in oncology · 2022Article
- TNF-induced necroptosis initiates early autophagy events via RIPK3-dependent AMPK activation, but inhibits late autophagy.Autophagy · 2021Article
- A novel PGAM5 inhibitor LFHP-1c protects blood-brain barrier integrity in ischemic stroke.Acta pharmaceutica Sinica. B · 2021Article
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThe AMP-activated protein kinase (AMPK) plays critical roles in growth regulation and metabolism reprogramming. AMPK activation protects cells against apoptosis from injury in different cell and animal models. However, its function in necroptosis remains largely unclear. METHODS AND
resultsIn the current study, we demonstrated that AMPK was activated upon necroptosis induction and protected mouse embryonic fibroblasts (MEFs) and cardiomyocytes from N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and reactive oxygen species (ROS) induced necroptosis. Activation of AMPK with chemicals A-769662, 2-deoxyglucose (2-DG), and metformin or constitutively active (CA) AMPK markedly decreased necroptosis and cytotoxicity induced by MNNG. In contrast, AMPK inhibitor compound C, dominant negative (DN) AMPK, as well as AMPK shRNAs increased necroptosis and cytotoxicity induced by MNNG. We further showed that AMPK physically associated with a protein complex containing PGAM5 and Keap1 whereby facilitating Keap1-mediated PGAM5 ubiquitination upon necroptosis induction. The AMPK agonist metformin ameliorated myocardial ischemia and reperfusion (IR) injury and reduced necroptosis through down-regulating the expression of PGAM5 in the Langendorff-perfused rat hearts.
conclusionActivation of AMPK protects against necroptosis via promoting Keap1-mediated PGAM5 degradation. Metformin may act as a valuable agent for the protection of myocardial ischemia and reperfusion injury by activating AMPK and reducing necroptosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.