ArticleDiabetes2013
Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Copper, cuproptosis, and cancer: biology concepts of a novel cell death.Apoptosis : an international journal on programmed cell death · 2026Review
- Copper Metabolism in Isolated Macrophages: Regulator of Immunity and Inflammation.Veterinary sciences · 2026Review
- Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Research progress of copper in diabetes and diabetic kidney disease: a narrative review.Frontiers in endocrinology · 2025Review
- The role of dysregulated copper metabolism in diabetes and its complications: a review.Frontiers in endocrinology · 2025Review
- Copper Dyshomeostasis and Diabetic Complications: Chelation Strategies for Management.Mini reviews in medicinal chemistry · 2025Review
- The Molecular Mechanisms of Cuproptosis and Small-Molecule Drug Design in Diabetes Mellitus.Molecules (Basel, Switzerland) · 2024Review
- Mapping novel QTL and fine mapping of previously identified QTL associated with glucose tolerance using the collaborative cross mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- Cuproptosis: potential new direction in diabetes research and treatment.Frontiers in endocrinology · 2024Review
- Exercise improves angiogenic function of circulating exosomes in type 2 diabetes: Role of exosomal SOD3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- The Molecular Mechanisms of Defective Copper Metabolism in Diabetic Cardiomyopathy.Oxidative medicine and cellular longevity · 2022Review
- Melatonin Improves Levels of Zn and Cu in the Muscle of Diabetic Obese Rats.Pharmaceutics · 2021Article
- The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2.Nature communications · 2021Article
- Superoxide Dismutase 1 in Health and Disease: How a Frontline Antioxidant Becomes Neurotoxic.Angewandte Chemie (International ed. in English) · 2021Review
- Caveolin-1 stabilizes ATP7A, a copper transporter for extracellular SOD, in vascular tissue to maintain endothelial function.American journal of physiology. Cell physiology · 2020Article
- The molecular mechanisms of copper metabolism and its roles in human diseases.Pflugers Archiv : European journal of physiology · 2020Review
- Anti-oxidative effects of superoxide dismutase 3 on inflammatory diseases.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Copper Transporter ATP7A (Copper-Transporting P-Type ATPase/Menkes ATPase) Limits Vascular Inflammation and Aortic Aneurysm Development: Role of MicroRNA-125b.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Copper transporters and copper chaperones: roles in cardiovascular physiology and disease.American journal of physiology. Cell physiology · 2018Review
- Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Oxidative stress and endothelial dysfunction contribute to vascular complication in diabetes. Extracellular superoxide dismutase (SOD3) is one of the key antioxidant enzymes that obtains copper via copper transporter ATP7A. SOD3 is secreted from vascular smooth muscles cells (VSMCs) and anchors at the endothelial surface. The role of SOD3 and ATP7A in endothelial dysfunction in type 1 diabetes mellitus (T1DM) is entirely unknown. Here we show that the specific activity of SOD3, but not SOD1, is decreased, which is associated with increased O2(•-) production in aortas of streptozotocin-induced and genetically induced Ins2(Akita) T1DM mice. Exogenous copper partially rescued SOD3 activity in isolated T1DM vessels. Functionally, acetylcholine-induced, endothelium-dependent relaxation is impaired in T1DM mesenteric arteries, which is rescued by SOD mimetic tempol or gene transfer of SOD3. Mechanistically, ATP7A expression in T1DM vessels is dramatically decreased whereas other copper transport proteins are not altered. T1DM-induced endothelial dysfunction and decrease of SOD3 activity are rescued in transgenic mice overexpressing ATP7A. Furthermore, SOD3-deficient T1DM mice or ATP7A mutant T1DM mice augment endothelial dysfunction and vascular O2(•-) production versus T1DM mice. These effects are in part due to hypoinsulinemia in T1DM mice, since insulin treatment, but not high glucose, increases ATP7A expression in VSMCs and restores SOD3 activity in the organoid culture of T1DM vessels. In summary, a decrease in ATP7A protein expression contributes to impaired SOD3 activity, resulting in O2(•-) overproduction and endothelial dysfunction in blood vessels of T1DM. Thus, restoring copper transporter function is an essential therapeutic approach for oxidant stress-dependent vascular and metabolic diseases.
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Registered trials
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.