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 journalArticle

35 Citations (Scopus)

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

Fingerprint

Cardiomyopathies
Phosphoric Monoester Hydrolases
Ischemia
Phosphorylation
MAP Kinase Kinase Kinase 5
Peptidylprolyl Isomerase
Ketone Bodies
Proteins
Metabolomics
Citric Acid Cycle
Extracellular Signal-Regulated MAP Kinases
Dilated Cardiomyopathy
p38 Mitogen-Activated Protein Kinases
Glycolysis
Aspartic Acid
Proteomics
Dilatation
Heart Diseases
Down-Regulation
Tensins

Keywords

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

ASJC Scopus subject areas

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

Cite this

Association of DJ-1/PTEN/AKT- and ASK1/p38-mediated cell signalling with ischaemic cardiomyopathy. / Klawitter, Jelena; Klawitter, Jost; Agardi, Erika; Corby, Kyler; Leibfritz, Dieter; Lowes, Brian D; Christians, Uwe; Seres, Tamas.

In: Cardiovascular research, Vol. 97, No. 1, 01.01.2013, p. 66-76.

Research output: Contribution to journalArticle

Klawitter, J, Klawitter, J, Agardi, E, Corby, K, Leibfritz, D, Lowes, BD, Christians, U & Seres, T 2013, 'Association of DJ-1/PTEN/AKT- and ASK1/p38-mediated cell signalling with ischaemic cardiomyopathy', Cardiovascular research, vol. 97, no. 1, pp. 66-76. https://doi.org/10.1093/cvr/cvs302
Klawitter, Jelena ; Klawitter, Jost ; Agardi, Erika ; Corby, Kyler ; Leibfritz, Dieter ; Lowes, Brian D ; Christians, Uwe ; Seres, Tamas. / Association of DJ-1/PTEN/AKT- and ASK1/p38-mediated cell signalling with ischaemic cardiomyopathy. In: Cardiovascular research. 2013 ; Vol. 97, No. 1. pp. 66-76.
@article{d4e4b24cd65048b0af0ed5f493c97b0c,
title = "Association of DJ-1/PTEN/AKT- and ASK1/p38-mediated cell signalling with ischaemic cardiomyopathy",
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.",
keywords = "Cardiomyopathy, Cell signaling, IDCM, ISCM, Metabolomics, Proteomics",
author = "Jelena Klawitter and Jost Klawitter and Erika Agardi and Kyler Corby and Dieter Leibfritz and Lowes, {Brian D} and Uwe Christians and Tamas Seres",
year = "2013",
month = "1",
day = "1",
doi = "10.1093/cvr/cvs302",
language = "English (US)",
volume = "97",
pages = "66--76",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Association of DJ-1/PTEN/AKT- and ASK1/p38-mediated cell signalling with ischaemic cardiomyopathy

AU - Klawitter, Jelena

AU - Klawitter, Jost

AU - Agardi, Erika

AU - Corby, Kyler

AU - Leibfritz, Dieter

AU - Lowes, Brian D

AU - Christians, Uwe

AU - Seres, Tamas

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

KW - Cardiomyopathy

KW - Cell signaling

KW - IDCM

KW - ISCM

KW - Metabolomics

KW - Proteomics

UR - http://www.scopus.com/inward/record.url?scp=84871792813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871792813&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvs302

DO - 10.1093/cvr/cvs302

M3 - Article

C2 - 23015639

AN - SCOPUS:84871792813

VL - 97

SP - 66

EP - 76

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 1

ER -