ArticleFree radical biology & medicine2013
Folic acid reverses nitric oxide synthase uncoupling and prevents cardiac dysfunction in insulin resistance: role of Ca2+/calmodulin-activated protein kinase II.
Article in Free radical biology & medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Primordial Drivers of Diabetes Heart Disease: Comprehensive Insights into Insulin Resistance.Diabetes & metabolism journal · 2024Review
- Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging.Archives of toxicology · 2023Review
- Pro-Apoptotic Activity of Bioactive Compounds from Seaweeds: Promising Sources for Developing Novel Anticancer Drugs.Marine drugs · 2023Review
- The functions of CaJournal of cell communication and signaling · 2023Review
- Biopterin metabolism and nitric oxide recoupling in cancer.Frontiers in oncology · 2023Review
- Type 2 Diabetes Complicated With Heart Failure: Research on Therapeutic Mechanism and Potential Drug Development Based on Insulin Signaling Pathway.Frontiers in pharmacology · 2022Review
- Folic Acid Alleviates High Glucose and Fat-Induced Pyroptosis via Inhibition of the Hippo Signal Pathway on H9C2 Cells.Frontiers in molecular biosciences · 2021Article
- Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats.Cell calcium · 2020Article
- Angiotensin II Decreases Endothelial Nitric Oxide Synthase PhosphorylationFrontiers in physiology · 2020Article
- Sepiapterin Enhances Tumor Radio- and Chemosensitivities by Promoting Vascular Normalization.The Journal of pharmacology and experimental therapeutics · 2018Article
- The cryoprotectant trehalose could inhibit ERS-induced apoptosis by activating autophagy in cryoprotected rat valves.PloS one · 2018Article
- High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy.Oxidative medicine and cellular longevity · 2017Article
- Mitochondrial aldehyde dehydrogenase obliterates insulin resistance-induced cardiac dysfunction through deacetylation of PGC-1α.Oncotarget · 2016Article
- mTOR-Independent autophagy inducer trehalose rescues against insulin resistance-induced myocardial contractile anomalies: Role of p38 MAPK and Foxo1.Pharmacological research · 2016Article
- Cardiomyocyte GTP Cyclohydrolase 1 Protects the Heart Against Diabetic Cardiomyopathy.Scientific reports · 2016Article
- ROS and ROS-Mediated Cellular Signaling.Oxidative medicine and cellular longevity · 2016Review
- The effect of B vitamin supplementation on wound healing in type 2 diabetic mice.Journal of clinical biochemistry and nutrition · 2016Article
- Activation of M3 cholinoceptors attenuates vascular injury after ischaemia/reperfusion by inhibiting the Ca2+/calmodulin-dependent protein kinase II pathway.British journal of pharmacology · 2015Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Nitric oxide synthase (NOS) may be uncoupled to produce superoxide rather than nitric oxide (NO) under pathological conditions such as diabetes mellitus and insulin resistance, leading to cardiac contractile anomalies. Nonetheless, the role of NOS uncoupling in insulin resistance-induced cardiac dysfunction remains elusive. Given that folic acid may produce beneficial effects for cardiac insufficiency partially through its NOS recoupling capacity, this study was designed to evaluate the effect of folic acid on insulin resistance-induced cardiac contractile dysfunction in a sucrose-induced insulin resistance model. Mice were fed a sucrose or starch diet for 8 weeks before administration of folic acid in drinking water for an additional 4 weeks. Cardiomyocyte contractile and Ca(2+) transient properties were evaluated and myocardial function was assessed using echocardiography. Our results revealed whole body insulin resistance after sucrose feeding associated with diminished NO production, elevated peroxynitrite (ONOO(-)) levels, and impaired echocardiographic and cardiomyocyte function along with a leaky ryanodine receptor (RYR) and intracellular Ca(2+) handling derangement. Western blot analysis showed that insulin resistance significantly promoted Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation, which might be responsible for the leaky RYR and cardiac mechanical dysfunction. NOS recoupling using folic acid reversed insulin resistance-induced changes in NO and ONOO(-), CaMKII phosphorylation, and cardiac mechanical abnormalities. Taken together, these data demonstrated that treatment with folic acid may reverse cardiac contractile and intracellular Ca(2+) anomalies through ablation of CaMKII phosphorylation and RYR Ca(2+) leak.
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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.