| 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: MEDLINE |
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; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-01-13 |
Journal Detail:
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Title: Journal of vascular research Volume: 49 ISSN: 1423-0135 ISO Abbreviation: J. Vasc. Res. Publication Date: 2012 |
Date Detail:
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Created Date: 2012-04-04 Completed Date: 2012-06-04 Revised Date: 2013-05-22 |
Medline Journal Info:
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Nlm Unique ID: 9206092 Medline TA: J Vasc Res Country: Switzerland |
Other Details:
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Languages: eng Pagination: 89-100 Citation Subset: IM |
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. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylglucosamine
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pharmacology* Carnitine O-Palmitoyltransferase / antagonists & inhibitors Epoxy Compounds / pharmacology Fatty Acids / metabolism* Heat-Shock Proteins / biosynthesis* Human Umbilical Vein Endothelial Cells Humans Mitochondria / drug effects, metabolism Nanofibers Oxidation-Reduction PPAR gamma / metabolism Protein Kinases / biosynthesis Protein-Serine-Threonine Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism* Transcription Factors / biosynthesis* Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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F30 DE021612/DE/NIDCR NIH HHS; R01 HL84565/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Epoxy Compounds; 0/Fatty Acids; 0/Heat-Shock Proteins; 0/PPAR gamma; 0/PPARGC1A protein, human; 0/Transcription Factors; 0/poly-N-acetyl glucosamine; 7512-17-6/Acetylglucosamine; EC 2.3.1.21/Carnitine O-Palmitoyltransferase; EC 2.7.-/Protein Kinases; EC 2.7.1.-/integrin-linked kinase; EC 2.7.1.-/pyruvate dehydrogenase kinase 4; EC 2.7.11.1/AKT1 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; MSB3DD2XP6/etomoxir |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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