title: Integrin-dependent Akt1 activation regulates PGC-1 expression and fatty acid oxidation.
abstract: 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.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, S.C., USA.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Beeson
authors.forename: Gyda C
authors.initials: GC
authors.lastname: Beeson
authors.forename: Haley
authors.initials: H
authors.lastname: Buff
authors.forename: Juanita
authors.initials: J
authors.lastname: Eldridge
authors.forename: Aiguo
authors.initials: A
authors.lastname: Zhang
authors.forename: Arun
authors.initials: A
authors.lastname: Seth
authors.forename: Marina
authors.initials: M
authors.lastname: Demcheva
authors.forename: John N
authors.initials: JN
authors.lastname: Vournakis
authors.forename: Robin C
authors.initials: RC
authors.lastname: Muise-Helmericks
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology*; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D057139:Nanofibers; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011494:Protein Kinases / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation; D000099200:Scaffold Protein ILK
chemical_list: D000117:Acetylglucosamine; D002334:Carnitine O-Palmitoyltransferase; D004852:Epoxy Compounds; D005227:Fatty Acids; D006360:Heat-Shock Proteins; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; D000099200:Scaffold Protein ILK; C486497:PPARGC1A protein, human; C113831:poly-N-acetyl glucosamine; C403287:pyruvate dehydrogenase kinase 4; C494918:AKT1 protein, human; C054207:etomoxir