| Cardiac phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase increases glycolysis, hypertrophy, and myocyte resistance to hypoxia. | |
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MedLine Citation:
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PMID: 18456722 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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During ischemia and heart failure, there is an increase in cardiac glycolysis. To understand if this is beneficial or detrimental to the heart, we chronically elevated glycolysis by cardiac-specific overexpression of phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) in transgenic mice. PFK-2 controls the level of fructose-2,6-bisphosphate (Fru-2,6-P2), an important regulator of phosphofructokinase and glycolysis. Transgenic mice had over a threefold elevation in levels of Fru-2,6-P2. Cardiac metabolites upstream of phosphofructokinase were significantly reduced, as would be expected by the activation of phosphofructokinase. In perfused hearts, the transgene caused a significant increase in glycolysis that was less sensitive to inhibition by palmitate. Conversely, oxidation of palmitate was reduced by close to 50%. The elevation in glycolysis made isolated cardiomyocytes highly resistant to contractile inhibition by hypoxia, but in vivo the transgene had no effect on ischemia-reperfusion injury. Transgenic hearts exhibited pathology: the heart weight-to-body weight ratio was increased 17%, cardiomyocyte length was greater, and cardiac fibrosis was increased. However, the transgene did not change insulin sensitivity. These results show that the elevation in glycolysis provides acute benefits against hypoxia, but the chronic increase in glycolysis or reduction in fatty acid oxidation interferes with normal cardiac metabolism, which may be detrimental to the heart. |
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Authors:
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Qianwen Wang; Rajakumar V Donthi; Jianxun Wang; Alex J Lange; Lewis J Watson; Steven P Jones; Paul N Epstein |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-05-02 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 294 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-06-09 Completed Date: 2008-08-15 Revised Date: 2011-05-03 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H2889-97 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Hypoxia Disease Models, Animal Glycolysis* Hypertrophy Insulin / metabolism Male Mice Mice, Transgenic Muscle Contraction Mutation* Myocardial Infarction / enzymology Myocardial Reperfusion Injury / enzymology*, pathology Myocardium / enzymology*, pathology Myocytes, Cardiac / enzymology Oxidation-Reduction Palmitic Acid / metabolism Phosphofructokinase-2 / genetics, metabolism* Time Factors Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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DK-073586/DK/NIDDK NIH HHS; HL-62892/HL/NHLBI NIH HHS; HL-83320/HL/NHLBI NIH HHS; R01 HL094419-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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11061-68-0/Insulin; 57-10-3/Palmitic Acid; EC 2.7.1.105/Phosphofructokinase-2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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