title: Association of DJ-1/PTEN/AKT- and ASK1/p38-mediated cell signalling with ischaemic cardiomyopathy.
abstract: OBJECTIVE
  Dilated cardiomyopathies from chronic ischaemia (ISCM) or idiopathic (IDCM) pathological mechanisms are accompanied by similar clinical symptoms but may differ in protein expression, cell metabolism, and signalling processes at the cellular level. Using a combination of proteomic and metabolomic profiling, we sought to decipher the relationships between the metabolism and cellular signalling pathways in human heart tissues collected from patients with ISCM, IDCM, and those without heart disease and dilation.
  
  
  RESULTS
  The comparative analysis suggested a decrease in glycolysis, Krebs cycle, and malate-aspartate shuttle activities in both types of cardiomyopathies and an increase in ketone body oxidation only in ISCM. Chronic ischaemic injury was associated with increased DJ-1 and decreased phosphatase and tensin homolog (PTEN) protein expression. The reduced PTEN expression was accompanied by increased phosphorylation of cell-protective AKT. Phosphorylation at T845 of apoptosis signal-regulating kinase 1 and p38 mitogen-activated protein kinase proteins, with no change in the phosphorylation of extracellular signal-regulated kinases, was also observed. The downregulation of peptidyl-prolyl cis/trans isomerase and NF-κB essential modulator potentially inhibits NF-κB-initiated processes.
  
  
  CONCLUSIONS
  The present study characterized differences in the molecular mechanisms, metabolism, and pathological cell signalling associated with ISCM and IDCM, which may provide novel targets for intervention at the cellular level.
authors.affiliation: Clinical Research and Development, Department of Anesthesiology, University of Colorado Denver, 1999 N. Fitzsimons Parkway Bioscience East, Suite 100, Aurora, CO 80045-7503, USA. jelena.klawitter@ucdenver.edu
authors.forename: Jelena
authors.initials: J
authors.lastname: Klawitter
authors.forename: Jost
authors.initials: J
authors.lastname: Klawitter
authors.forename: Erika
authors.initials: E
authors.lastname: Agardi
authors.forename: Kyler
authors.initials: K
authors.lastname: Corby
authors.forename: Dieter
authors.initials: D
authors.lastname: Leibfritz
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lowes
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
authors.forename: Tamas
authors.initials: T
authors.lastname: Seres
mesh_terms: D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D003599:Cytoskeleton / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D048848:MAP Kinase Kinase Kinase 5 / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D015513:Oncogene Proteins / Q000032:analysis*; D018384:Oxidative Stress; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D010766:Phosphorylation; D000071617:Protein Deglycase DJ-1; D040901:Proteomics / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human