Document Detail


Integrin-Dependent Akt1 Activation Regulates PGC-1 Expression and Fatty Acid Oxidation.
MedLine Citation:
PMID:  22249024     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  JOURNAL ARTICLE     Date:  2012-1-13
Journal Detail:
Title:  Journal of vascular research     Volume:  49     ISSN:  1423-0135     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9206092     Medline TA:  J Vasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  89-100     Citation Subset:  -    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Affiliation:
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, S.C., USA.
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