Association of DJ-1/PTEN/AKT- and ASK1/p38-mediated cell signalling with ischaemic cardiomyopathy

Jelena Klawitter, Jost Klawitter, Erika Agardi, Kyler Corby, Dieter Leibfritz, Brian D. Lowes, Uwe Christians, Tamas Seres

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Aims 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.Methods and resultsThe 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.ConclusionThe 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.

Original languageEnglish (US)
Pages (from-to)66-76
Number of pages11
JournalCardiovascular research
Volume97
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Cardiomyopathy
  • Cell signaling
  • IDCM
  • ISCM
  • Metabolomics
  • Proteomics

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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