ArticleBiochimica et biophysica acta2015
Mild hypoxia in vivo regulates cardioprotective SUR2A: A role for Akt and LDH.
Article in Biochimica et biophysica acta, 2015. 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.
- Cardioprotective Signaling: Outline and Future Directions.Biomedicines · 2025Review
- Review
- Recent Developments in Protein Lactylation in PTSD and CVD: Novel Strategies and Targets.Biotech (Basel (Switzerland)) · 2023Review
- SUR2A as a base for cardioprotective therapeutic strategies.Molecular biology reports · 2022Review
- Regulating glycolysis and heat shock proteins in Gannan yaks (Archives animal breeding · 2021Article
- The involvement of protein kinases in the cardioprotective effect of chronic hypoxia.Physiological research · 2020Review
- Cardioprotection by isosteviol derivate JC105: A unique drug property to activate ERK1/2 only when cells are exposed to hypoxia-reoxygenation.Journal of cellular and molecular medicine · 2020Article
- Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy.Biochemistry and biophysics reports · 2018Article
- Exposure to 15% oxygen in vivo up-regulates cardioprotective SUR2A without affecting ERK1/2 and AKT: a crucial role for AMPK.Journal of cellular and molecular medicine · 2017Article
- Supporting the One-Carbon Cycle Restores Ovarian Reserve in Subfertile Women: Absence of Correlation with Urinary Bisphenol A Concentration.BioResearch open access · 2017Article
- SNPs, linkage disequilibrium, and chronic mountain sickness in Tibetan Chinese.Hypoxia (Auckland, N.Z.) · 2017Article
- Neuroprotective Strategies during Cardiac Surgery with Cardiopulmonary Bypass.International journal of molecular sciences · 2016Review
- Anti-Apoptotic and Pro-Survival Effect of Alpinate Oxyphyllae Fructus (AOF) in a d-Galactose-Induced Aging Heart.International journal of molecular sciences · 2016Article
- A spontaneous increase in intracellular Ca2+ in metaphase II human oocytes in vitro can be prevented by drugs targeting ATP-sensitive K+ channels.Human reproduction (Oxford, England) · 2016Article
- ATP Sensitive Potassium Channels in the Skeletal Muscle Function: Involvement of the KCNJ11(Kir6.2) Gene in the Determination of Mechanical Warner Bratzer Shear Force.Frontiers in physiology · 2016Review
- Phenylephrine preconditioning in embryonic heart H9c2 cells is mediated by up-regulation of SUR2B/Kir6.2: A first evidence for functional role of SUR2B in sarcolemmal KATP channels and cardioprotection.The international journal of biochemistry & cell biology · 2016Article
- CREB Negatively Regulates IGF2R Gene Expression and Downstream Pathways to Inhibit Hypoxia-Induced H9c2 Cardiomyoblast Cell Death.International journal of molecular sciences · 2015Article
- A link between ATP and SUR2A: A novel mechanism explaining cardioprotection at high altitude.International journal of cardiology · 2015Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
High-altitude residents have lower mortality rates for ischaemic heart disease and this is ascribed to cardiac gene remodelling by chronic hypoxia. SUR2A is a cardioprotective ABC protein serving as a subunit of sarcolemmal ATP-sensitive K(+) channels. The purpose of this study was to determine whether SUR2A is regulated by mild hypoxia in vivo and to elucidate the underlying mechanism. Mice were exposed to either 21% (control) or 18% (mild hypoxia) oxygen for 24h. Exposure to 18% oxygen did not affect partial pressure of O(2) (PO(2)) and CO(2) (PCO(2)) in the blood, haematocrit or level of ATP in the heart. However, hypoxia increased myocardial lactate dehydrogenase (LDH) and lactate as well as NAD(+) without affecting total NAD. SUR2A levels were significantly increased as well as myocardial resistance to ischaemia-reperfusion. Exposure to 18% oxygen did not phosphorylate extracellular signal regulated kinases (ERK1/2) or AMP activated protein kinase (AMPK), but it phosphorylated protein kinase B (Akt). An inhibitor of phosphoinositide 3-kinases (PI3K), LY294002 (0.2mg/mouse), abolished all observed effects of hypoxia. LDH inhibitors, galloflavin (50 μM) and sodium oxamate (80 mM) significantly decreased levels of SUR2A in heart embryonic H9c2 cells, while inactive mutant LDH form, gly193-M-LDH increased cellular sensitivity towards stress induced by 2,4-dinitrophenol (10mM). Treatment of H9c2 cells with sodium lactate (30 mM) increased intracellular lactate, but did not affect LDH activity or SUR2A levels. We conclude that PI3K/Akt signalling pathway and LDH play a crucial role in increase of cardiac SUR2A induced by in vivo exposure to 18% oxygen.
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