Document Detail


Integrin-dependent Akt1 activation regulates PGC-1 expression and fatty acid oxidation.
MedLine Citation:
PMID:  22249024     Owner:  NLM     Status:  MEDLINE    
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; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-13
Journal Detail:
Title:  Journal of vascular research     Volume:  49     ISSN:  1423-0135     ISO Abbreviation:  J. Vasc. Res.     Publication Date:  2012  
Date Detail:
Created Date:  2012-04-04     Completed Date:  2012-06-04     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  9206092     Medline TA:  J Vasc Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  89-100     Citation Subset:  IM    
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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MeSH Terms
Descriptor/Qualifier:
Acetylglucosamine / 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:
F30 DE021612/DE/NIDCR NIH HHS; R01 HL84565/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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
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