ArticleAmerican journal of respiratory cell and molecular biology2014
Endothelin-1 induces a glycolytic switch in pulmonary arterial endothelial cells via the mitochondrial translocation of endothelial nitric oxide synthase.
Article in American journal of respiratory cell and molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
- Activin A-Endothelin-1 Axis Governs Pulmonary Vascular Remodeling: Mechanistic Basis for Emerging Therapies in PAH.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Inhibition of PGK1 ameliorates acute kidney injury through inactivating the PKM2/ALOX12/ferroptosis pathway in a study with male mice.Nature communications · 2025Article
- Single-Cell and Spatial Transcriptomics Identified Fatty Acid-Binding Proteins Controlling Endothelial Glycolytic and Arterial Programming in Pulmonary Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- The mitochondrial redistribution of ENOS is regulated by AKT1 and dimer status.Nitric oxide : biology and chemistry · 2024Article
- Review
- Evaluation of Glycolysis and Mitochondrial Function in Endothelial Cells Using the Seahorse Analyzer.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Mitochondrial hyperfusion induces metabolic remodeling in lung endothelial cells by modifying the activities of electron transport chain complexes I and III.Free radical biology & medicine · 2024Article
- Novel Relationship between Mitofusin 2-Mediated Mitochondrial Hyperfusion, Metabolic Remodeling, and Glycolysis in Pulmonary Arterial Endothelial Cells.International journal of molecular sciences · 2023Article
- Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2023Article
- Metabolic reprogramming, oxidative stress, and pulmonary hypertension.Redox biology · 2023Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Pulmonary Vascular Remodeling in Pulmonary Hypertension.Journal of personalized medicine · 2023Review
- The Impact of Tobacco Cigarettes, Vaping Products and Tobacco Heating Products on Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Review
- Review
- Mitochondrial Metabolism, Redox, and Calcium Homeostasis in Pulmonary Arterial Hypertension.Biomedicines · 2022Review
- Glucose-6-phosphate dehydrogenase and MEG3 controls hypoxia-induced expression of serum response factor (SRF) and SRF-dependent genes in pulmonary smooth muscle cell.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2022Article
- Endothelial upregulation of mechanosensitive channel Piezo1 in pulmonary hypertension.American journal of physiology. Cell physiology · 2021Article
- Endothelial cells in the pathogenesis of pulmonary arterial hypertension.The European respiratory journal · 2021Review
- Hepatic Knockdown of Endothelin Type A Receptor (ETAR) Ameliorates Hepatic Insulin Resistance and Hyperglycemia Through Suppressing p66Shc-Mediated Mitochondrial Fragmentation in High-Fat Diet-Fed Mice.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- NDUFA4L2 in smooth muscle promotes vascular remodeling in hypoxic pulmonary arterial hypertension.Journal of cellular and molecular medicine · 2021Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Recent studies have indicated that, during the development of pulmonary hypertension (PH), there is a switch from oxidative phosphorylation to glycolysis in the pulmonary endothelium. However, the mechanisms underlying this phenomenon have not been elucidated. Endothelin (ET)-1, an endothelial-derived vasoconstrictor peptide, is increased in PH, and has been shown to play an important role in the oxidative stress associated with PH. Thus, in this study, we investigated whether there was a potential link between increases in ET-1 and mitochondrial remodeling. Our data indicate that ET-1 induces the redistribution of endothelial nitric oxide synthase (eNOS) from the plasma membrane to the mitochondria in pulmonary arterial endothelial cells, and that this was dependent on eNOS uncoupling. We also found that ET-1 disturbed carnitine metabolism, resulting in the attenuation of mitochondrial bioenergetics. However, ATP levels were unchanged due to a compensatory increase in glycolysis. Further mechanistic investigations demonstrated that ET-1 mediated the redistribution of eNOS via the phosphorylation of eNOS at Thr495 by protein kinase C δ. In addition, the glycolytic switch appeared to be dependent on mitochondrial-derived reactive oxygen species that led to the activation of hypoxia-inducible factor signaling. Finally, the cell culture data were confirmed in vivo using the monocrotaline rat model of PH. Thus, we conclude that ET-1 induces a glycolytic switch in pulmonary arterial endothelial cells via the redistribution of uncoupled eNOS to the mitochondria, and that preventing this event may be an approach for the treatment of PH.
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