Myeloperoxidase impairs the contractile function in isolated human cardiomyocytes

Judit Kalász, Eniko T. Pásztor, Miklós Fagyas, Ágnes Balogh, Attila Tóth, Viktória Csató, I. Édes, Z. Papp, A. Borbély

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We set out to characterize the mechanical effects of myeloperoxidase (MPO) in isolated left-ventricular human cardiomyocytes. Oxidative myofilament protein modifications (sulfhydryl (SH)-group oxidation and carbonylation) induced by the peroxidase and chlorinating activities of MPO were additionally identified. The specificity of the MPO-evoked functional alterations was tested with an MPO inhibitor (MPO-I) and the antioxidant amino acid Met. The combined application of MPO and its substrate, hydrogen peroxide (H2O2), largely reduced the active force (Factive), increased the passive force (Fpassive), and decreased the Ca2+ sensitivity of force production (pCa50) in permeabilized cardiomyocytes. H2O2 alone had significantly smaller effects on Factive and Fpassive and did not alter pCa50. The MPO-I blocked both the peroxidase and the chlorinating activities, whereas Met selectively inhibited the chlorinating activity of MPO. All of the MPO-induced functional effects could be prevented by the MPO-I and Met. Both H2O2 alone and MPO + H2O2 reduced the SH content of actin and increased the carbonylation of actin and myosin-binding protein C to the same extent. Neither the SH oxidation nor the carbonylation of the giant sarcomeric protein titin was affected by these treatments. MPO activation induces a cardiomyocyte dysfunction by affecting Ca2+-regulated active and Ca2+-independent passive force production and myofilament Ca2+ sensitivity, independent of protein SH oxidation and carbonylation. The MPO-induced deleterious functional alterations can be prevented by the MPO-I and Met. Inhibition of MPO may be a promising therapeutic target to limit myocardial contractile dysfunction during inflammation.

Original languageEnglish
Pages (from-to)116-127
Number of pages12
JournalFree Radical Biology and Medicine
Volume84
DOIs
Publication statusPublished - Jul 1 2015

Fingerprint

Cardiac Myocytes
Peroxidase
Carbonylation
Myofibrils
Oxidation
Actins
Connectin
Microfilament Proteins
Proteins
Hydrogen Peroxide

Keywords

  • Antioxidants
  • Cardiomyocyte contractile function
  • Free radicals
  • Hydrogen peroxide
  • modifications
  • Myeloperoxidase
  • Oxidative posttranslational protein

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Myeloperoxidase impairs the contractile function in isolated human cardiomyocytes. / Kalász, Judit; Pásztor, Eniko T.; Fagyas, Miklós; Balogh, Ágnes; Tóth, Attila; Csató, Viktória; Édes, I.; Papp, Z.; Borbély, A.

In: Free Radical Biology and Medicine, Vol. 84, 01.07.2015, p. 116-127.

Research output: Contribution to journalArticle

Kalász, Judit ; Pásztor, Eniko T. ; Fagyas, Miklós ; Balogh, Ágnes ; Tóth, Attila ; Csató, Viktória ; Édes, I. ; Papp, Z. ; Borbély, A. / Myeloperoxidase impairs the contractile function in isolated human cardiomyocytes. In: Free Radical Biology and Medicine. 2015 ; Vol. 84. pp. 116-127.
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AU - Tóth, Attila

AU - Csató, Viktória

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AU - Papp, Z.

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