ArticleThe Journal of biological chemistry2003
Chronic mild hypoxia protects heart-derived H9c2 cells against acute hypoxia/reoxygenation by regulating expression of the SUR2A subunit of the ATP-sensitive K+ channel.
Article in The Journal of biological chemistry, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 92 citations in OpenAlex.
- AMPK Signalling in Heart Failure: From Metabolic Sensor to Context-Dependent Therapeutic Target.Biomedicines · 2026Review
- Glutathione Upregulates the Expression of KBioMed research international · 2023Article
- The effect of an adaptation to hypoxia on cardiac tolerance to ischemia/reperfusion.Journal of biomedical research · 2022Article
- SUR2A as a base for cardioprotective therapeutic strategies.Molecular biology reports · 2022Review
- Subcellular trafficking and endocytic recycling of KAmerican journal of physiology. Cell physiology · 2022Review
- Cardiac dysfunction in spontaneously hypertensive old rats is associated with a significant decrease of SUR2 expression.Molecular and cellular biochemistry · 2021Article
- Protective effect of nicotinamide and L-arginine against monocrotaline-induced pulmonary hypertension in rats: gender dependence.Pharmacological reports : PR · 2020Article
- 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
- Pyrazinamide may possess cardioprotective properties.The Journal of antibiotics · 2019Article
- 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
- The Citrus Flavanone Naringenin Protects Myocardial Cells against Age-Associated Damage.Oxidative medicine and cellular longevity · 2017Article
- Non-cell autonomous cues for enhanced functionality of human embryonic stem cell-derived cardiomyocytes via maturation of sarcolemmal and mitochondrial KScientific reports · 2016Article
- Upregulated ATF6 contributes to chronic intermittent hypoxia-afforded protection against myocardial ischemia/reperfusion injury.International journal of molecular medicine · 2016Article
- Anti-Apoptotic and Pro-Survival Effect of Alpinate Oxyphyllae Fructus (AOF) in a d-Galactose-Induced Aging Heart.International journal of molecular sciences · 2016Article
- KATP Channels in the Cardiovascular System.Physiological reviews · 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
- Mild hypoxia in vivo regulates cardioprotective SUR2A: A role for Akt and LDH.Biochimica et biophysica acta · 2015Article
- Upregulation of cardioprotective SUR2A by sub-hypoxic drop in oxygen.Biochimica et biophysica acta · 2014Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronic exposure to lower oxygen tension may increase cellular resistance to different types of acute metabolic stress. Here, we show that 24-h-long exposure to slightly decreased oxygen tension (partial pressure of oxygen (PO2) of 100 mm Hg instead of normal 144 mm Hg) confers resistance against acute hypoxia/reoxygenation-induced Ca2+ loading in heart-derived H9c2 cells. The number of ATP-sensitive K+ (K(ATP)) channels were increased in cells exposed to PO2 = 100 mm Hg relative to cells exposed to PO2 = 144 mm Hg. This was due to an increase in transcription of SUR2A, a K(ATP) channel regulatory subunit, but not Kir6.2, a K(ATP) channel pore-forming subunit. PO2 = 100 mm Hg also increased the SUR2 gene promoter activity. Experiments with cells overexpressing wild type of hypoxia-inducible factor (HIF)-1alpha and dominant negative HIF-1beta suggested that the HIF-1-signaling pathway did not participate in observed PO2-mediated regulation of SUR2A expression. On the other hand, NADH inhibited the effect of PO2 = 100 mm Hg but not the effect of PO2 = 20 mm Hg. LY 294002 and PD 184 352 prevented PO2-mediated regulation of K(ATP) channels, whereas rapamycin was without any effect. HMR 1098 inhibited the cytoprotective effect of PO2 = 100 mm Hg, and a decrease of PO2 from 144 to 100 mm Hg did not change the expression of any other gene, including those involved in stress and hypoxic response, as revealed by Affymetrix high density oligonucleotide arrays. We conclude that slight hypoxia activates HIF-1alpha-independent signaling cascade leading to an increase in SUR2A protein, a higher density of K(ATP) channels, and a cellular phenotype more resistant to acute metabolic stress.
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