| Integrin-Dependent Akt1 Activation Regulates PGC-1 Expression and Fatty Acid Oxidation. | |
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MedLine Citation:
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PMID: 22249024 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background: Poly-N-acetyl glucosamine nanofibers derived from a marine diatom have been used to increase cutaneous wound healing. These nanofibers exert their activity by specifically activating integrins, which makes them a useful tool for dissecting integrin-mediated pathways. We have shown that short-fiber poly-N-acetyl glucosamine nanofiber (sNAG) treatment of endothelial cells results in increased cell motility and metabolic rate in the absence of increased cell proliferation. Results: Using a Seahorse Bioanalyzer to measure oxygen consumption in real time, we show that sNAG treatment increases oxygen consumption rates, correlated with an integrin-dependent activation of Akt1. Akt1 activation leads to an increase in the expression of the transcriptional coactivator, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). This is not due to increased mitochondrial biogenesis, but is associated with an increase in the expression of pyruvate dehydrogenase kinase 4 (PDK4), suggesting regulation of fatty acid oxidation. Blockade of fatty acid oxidation with etomoxir, an O-carnitine palmitoyltransferase-1 inhibitor, blocks the sNAG-dependent increased oxygen consumption. (3)H-palmitate uptake experiments indicate a PDK4-dependent increase in fatty acid oxidation, which is required for nanofiber-induced cell motility. Conclusions: Our findings imply a linear pathway whereby an integrin-dependent activation of Akt1 leads to increased PGC-1α and PDK4 expression resulting in increased energy production by fatty acid oxidation. |
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Authors:
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Craig C Beeson; Gyda C Beeson; Haley Buff; Juanita Eldridge; Aiguo Zhang; Arun Seth; Marina Demcheva; John N Vournakis; Robin C Muise-Helmericks |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-13 |
Journal Detail:
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Title: Journal of vascular research Volume: 49 ISSN: 1423-0135 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9206092 Medline TA: J Vasc Res Country: - |
Other Details:
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Languages: ENG Pagination: 89-100 Citation Subset: - |
Copyright Information:
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Copyright © 2012 S. Karger AG, Basel. |
Affiliation:
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Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, S.C., USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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