FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2014138859> ?p ?o ?g. }

• W2014138859 endingPage "76" @default.
• W2014138859 startingPage "73" @default.
• W2014138859 abstract "High altitude is defined as living at an altitude of 2400 m or more above sea level. It is well established that prevalence of ischaemic heart disease is decreased in people living at high altitude and that the mortality from this disease is lower in this cohort. Several potential explanations have been offered for the benefit of altitude on the frequency and outcome of ischemic heart disease. It has been shown that hypoxia induces molecular changes that have cardioprotective effect; this was ascribed largely to the actions of HIF-1, a transcription modulator, and up regulation of several genes including erythropoietin, vascular endothelial growth factor, NO synthase, and heme oxygenase-1 [[1]Hurtado A. Escudero E. Pando J. Sharma S. Johnson R.J. Cardiovascular and renal effects of chronic exposure to high altitude.Nephrol. Dial. Transplant. 2012; 27: iv11-iv16Crossref PubMed Scopus (44) Google Scholar]. In our previous studies we have shown that sub-hypoxic drop of oxygen as well as mild hypoxia up-regulate SUR2A and confer cardioprotection [2Mohammed Abdul K.S. Jovanović S. Du Q. Sukhodub A. Jovanović A. Upregulation of cardioprotective SUR2A by sub-hypoxic drop in oxygen.Biochim. Biophys. Acta, Mol. Cell Res. 2014; 1843: 2424-2431Crossref PubMed Scopus (20) Google Scholar, 3Mohammed Abdul K.S. Jovanović S. Du Q. Sukhodub A. Jovanović A. Mild hypoxia in vivo regulates cardioprotective SUR2A: a role for Akt and LDH.Biochim. Biophys. Acta Mol. Basis Dis. 2015; 1852: 709-719Crossref PubMed Scopus (25) Google Scholar]. SUR2A is an “atypical” ABC protein that binds to inward rectifier Kir6.2 to form cardiac sarcolemmal ATP-sensitive K+ channels. In vivo, KATP channels exist as a multiprotein complex that, besides pore-forming Kir6.1/Kir6.2 and regulatory SUR2A subunits, also contain a string of glycolytic and ATP-producing enzymes including creatine kinase, GAPDH and M-LDH. It has been shown that the changes in levels of SUR2A alone have a profound effect on hart development and myocardial susceptibility to different types of metabolic stresses including hypoxia, ischemia, ischemia–reperfusion and stimulation with β-adrenergic agonists [4Jovanović S. Mohammed Abdul K.S. Jovanović A. Cardioprotection afforded by SUR2A: an update.J. Cardiobiol. 2013; 1: 4Google Scholar, 5Land S. Walker D. Du Q. Jovanović A. Cardioprotective SUR2A promotes stem cell properties of cardiomyocytes.Int. J. Cardiol. 2013; 168: 5090-5092Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar]. Depending on the degree of oxygen decrease signaling pathway regulating SUR2A seems to be different. In a case of sub-hypoxic drop of oxygen, the activation of extracellular signal-regulated kinases (ERK) mediates up-regulation of SUR2A [[2]Mohammed Abdul K.S. Jovanović S. Du Q. Sukhodub A. Jovanović A. Upregulation of cardioprotective SUR2A by sub-hypoxic drop in oxygen.Biochim. Biophys. Acta, Mol. Cell Res. 2014; 1843: 2424-2431Crossref PubMed Scopus (20) Google Scholar]. On the other hand, ERK is not activated by mild hypoxia where, instead, protein kinase B (Akt) and lactate dehydrogenase (LDH) are activated to regulate SUR2A [[3]Mohammed Abdul K.S. Jovanović S. Du Q. Sukhodub A. Jovanović A. Mild hypoxia in vivo regulates cardioprotective SUR2A: a role for Akt and LDH.Biochim. Biophys. Acta Mol. Basis Dis. 2015; 1852: 709-719Crossref PubMed Scopus (25) Google Scholar]. Whether high altitude-hypoxia would regulate SUR2A levels and what the underlying mechanism would be is yet unknown. Normobaric 13% oxygen corresponds to oxygen tension at ~3600 m above sea level. 24 h-long general exposure of mice to 13% oxygen decreased PO2 without affecting PCO2 and hematocrit in the blood. In the myocardial tissue, hypoxia did not affect level of lactate dehydrogenase (LDH), but it increased lactate as well as NAD+. NADH in the myocardium was decreased while total NAD was not affected. Thus, exposure to 13% oxygen induced all expected signs of hypoxia in the blood and the heart. It has been shown that mild hypoxia increase levels of SUR2A and confer cardioprotection [[3]Mohammed Abdul K.S. Jovanović S. Du Q. Sukhodub A. Jovanović A. Mild hypoxia in vivo regulates cardioprotective SUR2A: a role for Akt and LDH.Biochim. Biophys. Acta Mol. Basis Dis. 2015; 1852: 709-719Crossref PubMed Scopus (25) Google Scholar]. Here, 13% oxygen in vivo also increased SUR2A in the myocardium (Fig. 1). Under physiological levels of oxygen, fatty acids serve as the major fuel substrate providing 60–80% of the heart energy requirements, while the rest is derived from glucose and lactate. During chronic hypoxia glucose uptake is enhanced and there is increased contribution of glucose/lactate in ATP production [[6]Essop M.F. Cardiac metabolic adaptations in response to hypoxia.J. Physiol. Lond. 2007; 584: 715-726Crossref Scopus (92) Google Scholar]. In vivo, it has been shown that severe hypoxia induces significant drop in myocardial ATP, while mild hypoxia does not affect ATP levels at all [[7]Portman M.A. Standaert T.A. Ning X.H. Relation of myocardial oxygen consumption and function to high energy phosphate utilization during graded hypoxia and reoxygenation in sheep in vivo.J. Clin. Invest. 1995; 95: 2134-2142Crossref PubMed Scopus (22) Google Scholar]. Here, we have found that systemic exposure to 13% oxygen significantly increased myocardial level of ATP (Fig. 1). Most of ATP produced in the heart is catalyzed by CK [[8]Stanley W.C. Recchia F.A. Lopaschuk G.D. Myocardial substrate metabolism in the normal and failing heart.Physiol. Rev. 2005; 85: 1093-1129Crossref PubMed Scopus (1480) Google Scholar]. Reduction in CK activity significantly reduces myocardial levels of ATP and it induces heart failure in both humans and experimental animals [[8]Stanley W.C. Recchia F.A. Lopaschuk G.D. Myocardial substrate metabolism in the normal and failing heart.Physiol. Rev. 2005; 85: 1093-1129Crossref PubMed Scopus (1480) Google Scholar]. On the other hand, increased level of CK is associated with increased levels of ATP [[9]Akki A. Su J. Yano T. Gupta A. Wang Y. Leppo M.K. Chacko V.P. Steenbergen C. Weiss R.G. Creatine kinase overexpression improves ATP kinetics and contractile function in postischemic myocardium.Am. J. Physiol. Heart Circ. Physiol. 2012; 303: H844-H852Crossref PubMed Scopus (30) Google Scholar]. Here we have measured levels of CK and found that exposure to 13% hypoxia significantly increased intracellular levels of CK (Fig. 1). Up-regulation of CK by chronic hypoxia has been recently reported [[10]Waskova-Arnostova P. Kasparova D. Elsnicova B. Novotny J. Neckar J. Kolar F. Zurmanova J. Chronic hypoxia enhances expression and activity of mitochondrial creatine kinase and hexokinase in the rat ventricular myocardium.Cell. Physiol. Biochem. 2014; 33: 310-320Crossref PubMed Scopus (24) Google Scholar] and our findings are in agreement with this report. An increased level of CK by hypoxia explains increased ATP in the heart we found. It has been shown in previous studies that sub-hypoxic drop of oxygen activates extracellular regulated kinases 1/2 (ERK1/2) and that mild hypoxia activates protein kinase B (Akt) to up-regulate SUR2A [2Mohammed Abdul K.S. Jovanović S. Du Q. Sukhodub A. Jovanović A. Upregulation of cardioprotective SUR2A by sub-hypoxic drop in oxygen.Biochim. Biophys. Acta, Mol. Cell Res. 2014; 1843: 2424-2431Crossref PubMed Scopus (20) Google Scholar, 3Mohammed Abdul K.S. Jovanović S. Du Q. Sukhodub A. Jovanović A. Mild hypoxia in vivo regulates cardioprotective SUR2A: a role for Akt and LDH.Biochim. Biophys. Acta Mol. Basis Dis. 2015; 1852: 709-719Crossref PubMed Scopus (25) Google Scholar]. 13% oxygen did not have any effect on ERK1/2 and Akt (data not shown), demonstrating that these kinases did not mediate observed increase in SUR2A. Akt is known to up-regulate LDH that, in turn, directly regulate expression of SUR2A [[3]Mohammed Abdul K.S. Jovanović S. Du Q. Sukhodub A. Jovanović A. Mild hypoxia in vivo regulates cardioprotective SUR2A: a role for Akt and LDH.Biochim. Biophys. Acta Mol. Basis Dis. 2015; 1852: 709-719Crossref PubMed Scopus (25) Google Scholar]. In the present study, 13% oxygen did not significantly affect LDH levels which further confirms that up-regulation of SUR2A was not associated with signaling pathway activated by 18% oxygen. ATP is a defining ligand of KATP channels and it is well established that this nucleotide regulates the channel activity [[4]Jovanović S. Mohammed Abdul K.S. Jovanović A. Cardioprotection afforded by SUR2A: an update.J. Cardiobiol. 2013; 1: 4Google Scholar]. SUR2A is a regulatory unit of KATP channels and a rate-limiting factor in formation of these channels [[4]Jovanović S. Mohammed Abdul K.S. Jovanović A. Cardioprotection afforded by SUR2A: an update.J. Cardiobiol. 2013; 1: 4Google Scholar]. Gating of KATP channels by ATP has been viewed as a link between membrane excitability and intracellular metabolism [[4]Jovanović S. Mohammed Abdul K.S. Jovanović A. Cardioprotection afforded by SUR2A: an update.J. Cardiobiol. 2013; 1: 4Google Scholar]. Here, we have examined whether a treatment known to alter intracellular ATP would have any effect on SUR2A levels and cellular resistance to stress. Embryonic rat heart H9c2 cells were treated by 2-deoxyglucose and this treatment 1) decreased intracellular ATP, 2) decreased SUR2A levels and 3) decreased cellular resistance to stress (Fig. 2). These results were compatible with the notion that intracellular ATP regulates SUR2A levels. To further test this hypothesis, we have applied DFNB, an inhibitor of CK. When DFNB was used in a concentration that did not affect intracellular ATP levels, SUR2A levels were also not affected (Fig. 2). On the other hand, when DFNB was applied in a concentration that decreased ATP, it also decreased SUR2A levels (Fig. 2). These findings strongly suggest that intracellular ATP regulate levels of SUR2A in the heart. Does ATP directly regulate SUR2A levels or whether it regulates ATP-depending factors regulating SUR2A has to be addressed in the future. In conclusion, this study has shown that hypoxia in vivo regulates level of cardioprotective SUR2A by regulating intracellular ATP. This is a previously unrecognized link between intracellular metabolism and cardioprotection. The authors report no relationships that could be construed as a conflict of interest." @default.
• W2014138859 created "2016-06-24" @default.
• W2014138859 creator A5005135256 @default.
• W2014138859 creator A5015865219 @default.
• W2014138859 creator A5020533673 @default.
• W2014138859 creator A5062857959 @default.
• W2014138859 creator A5069464640 @default.
• W2014138859 date "2015-06-01" @default.
• W2014138859 modified "2023-10-18" @default.
• W2014138859 title "A link between ATP and SUR2A: A novel mechanism explaining cardioprotection at high altitude" @default.
• W2014138859 cites W1504300847 @default.
• W2014138859 cites W1970164266 @default.
• W2014138859 cites W1972107647 @default.
• W2014138859 cites W1986420041 @default.
• W2014138859 cites W2049206904 @default.
• W2014138859 cites W2069067742 @default.
• W2014138859 cites W2071518542 @default.
• W2014138859 cites W2138842180 @default.
• W2014138859 cites W2147847000 @default.
• W2014138859 doi "https://doi.org/10.1016/j.ijcard.2015.04.069" @default.
• W2014138859 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4461008" @default.
• W2014138859 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25885875" @default.
• W2014138859 hasPublicationYear "2015" @default.
• W2014138859 type Work @default.
• W2014138859 sameAs 2014138859 @default.
• W2014138859 citedByCount "16" @default.
• W2014138859 countsByYear W20141388592015 @default.
• W2014138859 countsByYear W20141388592016 @default.
• W2014138859 countsByYear W20141388592017 @default.
• W2014138859 countsByYear W20141388592018 @default.
• W2014138859 countsByYear W20141388592019 @default.
• W2014138859 countsByYear W20141388592020 @default.
• W2014138859 countsByYear W20141388592022 @default.
• W2014138859 crossrefType "journal-article" @default.
• W2014138859 hasAuthorship W2014138859A5005135256 @default.
• W2014138859 hasAuthorship W2014138859A5015865219 @default.
• W2014138859 hasAuthorship W2014138859A5020533673 @default.
• W2014138859 hasAuthorship W2014138859A5062857959 @default.
• W2014138859 hasAuthorship W2014138859A5069464640 @default.
• W2014138859 hasBestOaLocation W20141388591 @default.
• W2014138859 hasConcept C105702510 @default.
• W2014138859 hasConcept C111472728 @default.
• W2014138859 hasConcept C126322002 @default.
• W2014138859 hasConcept C138885662 @default.
• W2014138859 hasConcept C164705383 @default.
• W2014138859 hasConcept C2778753846 @default.
• W2014138859 hasConcept C2779676291 @default.
• W2014138859 hasConcept C31258907 @default.
• W2014138859 hasConcept C41008148 @default.
• W2014138859 hasConcept C541997718 @default.
• W2014138859 hasConcept C71924100 @default.
• W2014138859 hasConcept C8240015 @default.
• W2014138859 hasConcept C89611455 @default.
• W2014138859 hasConcept C98274493 @default.
• W2014138859 hasConceptScore W2014138859C105702510 @default.
• W2014138859 hasConceptScore W2014138859C111472728 @default.
• W2014138859 hasConceptScore W2014138859C126322002 @default.
• W2014138859 hasConceptScore W2014138859C138885662 @default.
• W2014138859 hasConceptScore W2014138859C164705383 @default.
• W2014138859 hasConceptScore W2014138859C2778753846 @default.
• W2014138859 hasConceptScore W2014138859C2779676291 @default.
• W2014138859 hasConceptScore W2014138859C31258907 @default.
• W2014138859 hasConceptScore W2014138859C41008148 @default.
• W2014138859 hasConceptScore W2014138859C541997718 @default.
• W2014138859 hasConceptScore W2014138859C71924100 @default.
• W2014138859 hasConceptScore W2014138859C8240015 @default.
• W2014138859 hasConceptScore W2014138859C89611455 @default.
• W2014138859 hasConceptScore W2014138859C98274493 @default.
• W2014138859 hasLocation W20141388591 @default.
• W2014138859 hasLocation W20141388592 @default.
• W2014138859 hasLocation W20141388593 @default.
• W2014138859 hasLocation W20141388594 @default.
• W2014138859 hasLocation W20141388595 @default.
• W2014138859 hasLocation W20141388596 @default.
• W2014138859 hasOpenAccess W2014138859 @default.
• W2014138859 hasPrimaryLocation W20141388591 @default.
• W2014138859 hasRelatedWork W2021710766 @default.
• W2014138859 hasRelatedWork W2150736125 @default.
• W2014138859 hasRelatedWork W2329563008 @default.
• W2014138859 hasRelatedWork W2357490968 @default.
• W2014138859 hasRelatedWork W2372882120 @default.
• W2014138859 hasRelatedWork W2392625516 @default.
• W2014138859 hasRelatedWork W2689287298 @default.
• W2014138859 hasRelatedWork W2719157875 @default.
• W2014138859 hasRelatedWork W3136617963 @default.
• W2014138859 hasRelatedWork W58128503 @default.
• W2014138859 hasVolume "189" @default.
• W2014138859 isParatext "false" @default.
• W2014138859 isRetracted "false" @default.
• W2014138859 magId "2014138859" @default.
• W2014138859 workType "article" @default.