ArticleDiabetes2012
Reactive oxygen species signaling facilitates FOXO-3a/FBXO-dependent vascular BK channel β1 subunit degradation in diabetic mice.
Article in Diabetes, 2012. 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, 68 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Impact of Sorbs2 dysfunction on cardiovascular diseases.Biochimica et biophysica acta. Molecular basis of disease · 2025Review
- Glucagon-Like Peptide-1 Inhibits the Progression of Abdominal Aortic Aneurysm in Mice: The Earlier, the Better.Cardiovascular drugs and therapy · 2024Article
- Sorbs2 Deficiency and Vascular BK Channelopathy in Diabetes.Circulation research · 2024Article
- CaInternational journal of molecular sciences · 2023Review
- Oxidative Regulation of Vascular CaAntioxidants (Basel, Switzerland) · 2022Review
- Activating BK channels ameliorates vascular smooth muscle calcification through Akt signaling.Acta pharmacologica Sinica · 2022Article
- TMEM16A channel upregulation in arterial smooth muscle cells produces vasoconstriction during diabetes.American journal of physiology. Heart and circulatory physiology · 2021Article
- Coronary Large Conductance CaFrontiers in physiology · 2021Review
- Chronic Inhibition of mROS Protects Against Coronary Endothelial Dysfunction in Mice With Diabetes.Frontiers in cell and developmental biology · 2021Article
- Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle.Cellular and molecular life sciences : CMLS · 2021Review
- Gestational Hypoxia Inhibits Pregnancy-Induced Upregulation of CaHypertension (Dallas, Tex. : 1979) · 2020Article
- Developmental toxicity of carbon nanoparticles during embryogenesis in chicken.Environmental science and pollution research international · 2020Review
- Knockout of AKAP150 improves impaired BK channel-mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus.Journal of cellular and molecular medicine · 2020Article
- Regulation of KCNMA1 transcription by Nrf2 in coronary arterial smooth muscle cells.Journal of molecular and cellular cardiology · 2020Article
- BK Channel Dysfunction in Diabetic Coronary Artery: Role of the E3 Ubiquitin Ligases.Frontiers in physiology · 2020Review
- Impairment of amyloid precursor protein alpha-processing in cerebral microvessels of type 1 diabetic mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- F-box protein-32 down-regulates small-conductance calcium-activated potassium channel 2 in diabetic mouse atria.The Journal of biological chemistry · 2019Article
- Downregulation of BK channel function and protein expression in coronary arteriolar smooth muscle cells of type 2 diabetic patients.Cardiovascular research · 2019Article
- Effect of Oxidative Stress on the Estrogen-NOS-NO-KOxidative medicine and cellular longevity · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Activity of the vascular large conductance Ca(2+)-activated K(+) (BK) channel is tightly regulated by its accessory β(1) subunit (BK-β(1)). Downregulation of BK-β(1) expression in diabetic vessels is associated with upregulation of the forkhead box O subfamily transcription factor-3a (FOXO-3a)-dependent F-box-only protein (FBXO) expression. However, the upstream signaling regulating this process is unclear. Overproduction of reactive oxygen species (ROS) is a common finding in diabetic vasculopathy. We hypothesized that ROS signaling cascade facilitates the FOXO-3a/FBXO-mediated BK-β(1) degradation and leads to diabetic BK channel dysfunction. Using cellular biology, patch clamp, and videomicroscopy techniques, we found that reduced BK-β(1) expression in streptozotocin (STZ)-induced diabetic mouse arteries and in human coronary smooth muscle cells (SMCs) cultured with high glucose was attributable to an increase in protein kinase C (PKC)-β and NADPH oxidase expressions and accompanied by attenuation of Akt phosphorylation and augmentation of atrogin-1 expression. Treatment with ruboxistaurin (a PKCβ inhibitor) or with GW501516 (a peroxisome proliferator-activated receptor δ activator) reduced atrogin-1 expression and restored BK channel-mediated coronary vasodilation in diabetic mice. Our results suggested that oxidative stress inhibited Akt signaling and facilitated the FOXO-3a/FBXO-dependent BK-β(1) degradation in diabetic vessels. Suppression of the FOXO-3a/FBXO pathway prevented vascular BK-β(1) degradation and protected coronary function in diabetes.
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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.