Oxidation of myofilament protein sulfhydryl groups reduces the contractile force and its Ca2+ sensitivity in human cardiomyocytes

Zita Hertelendi, Attila Tóth, A. Borbély, Zoltán Galajda, Jolanda Van Der Velden, Ger J M Stienen, I. Édes, Z. Papp

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

This study sought to characterize the relation between the oxidation of protein sulfhydryl (SH) groups and Ca2+-activated force production in the human myocardium. Triton-permeabilized left ventricular cardiomyocytes from donor hearts were exposed to an oxidative (2,2′-dithiodipyridine, DTDP) agent in vitro, and the changes in isometric force, its Ca2+ sensitivity, the cross-bridge-sensitive rate constant of force redevelopment at saturating [Ca2+] (ktr,max), and protein SH oxidation were monitored. DTDP (0.1-10 mM for 2 min) oxidized the myocardial proteins and diminished the Ca2+-activated force with different concentration dependences (EC50,SH = 0.17 ± 0.02 mM and EC 50,force = 2.46 ± 0.22 mM; mean ± SEM). The application of 2.5 mM DTDP decreased the maximal Ca2+-activated force (to 64%), its Ca2+ sensitivity (ΔpCa50 = 0.22 ± 0.02), and the steepness of the Ca2+-force relation (nHill, from 2.01 ± 0.08 to 1.76 ± 0.08). These changes were paralleled by reductions in the free SH content of the proteins (to 15%) and in k tr,max (to 75%). SH-specific labeling identified SH oxidation of myosin light chain 1 and actin at DTDP concentrations at which the changes in the contractile parameters occurred. Our data suggest that SH oxidation in selected myofilament proteins diminishes the Ca2+-activated force and its Ca2+ sensitivity through an impaired Ca2+ regulation of the actin-myosin cycle in the human heart.

Original languageEnglish
Pages (from-to)1175-1184
Number of pages10
JournalAntioxidants and Redox Signaling
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 1 2008

Fingerprint

Myofibrils
Cardiac Myocytes
Oxidation
Actins
Proteins
Myosin Light Chains
Myosins
Labeling
Rate constants
Myocardium
Scanning electron microscopy

ASJC Scopus subject areas

  • Biochemistry

Cite this

Oxidation of myofilament protein sulfhydryl groups reduces the contractile force and its Ca2+ sensitivity in human cardiomyocytes. / Hertelendi, Zita; Tóth, Attila; Borbély, A.; Galajda, Zoltán; Van Der Velden, Jolanda; Stienen, Ger J M; Édes, I.; Papp, Z.

In: Antioxidants and Redox Signaling, Vol. 10, No. 7, 01.07.2008, p. 1175-1184.

Research output: Contribution to journalArticle

Hertelendi, Zita ; Tóth, Attila ; Borbély, A. ; Galajda, Zoltán ; Van Der Velden, Jolanda ; Stienen, Ger J M ; Édes, I. ; Papp, Z. / Oxidation of myofilament protein sulfhydryl groups reduces the contractile force and its Ca2+ sensitivity in human cardiomyocytes. In: Antioxidants and Redox Signaling. 2008 ; Vol. 10, No. 7. pp. 1175-1184.
@article{ddd071064afb4a78aa3fa696171cf20e,
title = "Oxidation of myofilament protein sulfhydryl groups reduces the contractile force and its Ca2+ sensitivity in human cardiomyocytes",
abstract = "This study sought to characterize the relation between the oxidation of protein sulfhydryl (SH) groups and Ca2+-activated force production in the human myocardium. Triton-permeabilized left ventricular cardiomyocytes from donor hearts were exposed to an oxidative (2,2′-dithiodipyridine, DTDP) agent in vitro, and the changes in isometric force, its Ca2+ sensitivity, the cross-bridge-sensitive rate constant of force redevelopment at saturating [Ca2+] (ktr,max), and protein SH oxidation were monitored. DTDP (0.1-10 mM for 2 min) oxidized the myocardial proteins and diminished the Ca2+-activated force with different concentration dependences (EC50,SH = 0.17 ± 0.02 mM and EC 50,force = 2.46 ± 0.22 mM; mean ± SEM). The application of 2.5 mM DTDP decreased the maximal Ca2+-activated force (to 64{\%}), its Ca2+ sensitivity (ΔpCa50 = 0.22 ± 0.02), and the steepness of the Ca2+-force relation (nHill, from 2.01 ± 0.08 to 1.76 ± 0.08). These changes were paralleled by reductions in the free SH content of the proteins (to 15{\%}) and in k tr,max (to 75{\%}). SH-specific labeling identified SH oxidation of myosin light chain 1 and actin at DTDP concentrations at which the changes in the contractile parameters occurred. Our data suggest that SH oxidation in selected myofilament proteins diminishes the Ca2+-activated force and its Ca2+ sensitivity through an impaired Ca2+ regulation of the actin-myosin cycle in the human heart.",
author = "Zita Hertelendi and Attila T{\'o}th and A. Borb{\'e}ly and Zolt{\'a}n Galajda and {Van Der Velden}, Jolanda and Stienen, {Ger J M} and I. {\'E}des and Z. Papp",
year = "2008",
month = "7",
day = "1",
doi = "10.1089/ars.2007.2014",
language = "English",
volume = "10",
pages = "1175--1184",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "7",

}

TY - JOUR

T1 - Oxidation of myofilament protein sulfhydryl groups reduces the contractile force and its Ca2+ sensitivity in human cardiomyocytes

AU - Hertelendi, Zita

AU - Tóth, Attila

AU - Borbély, A.

AU - Galajda, Zoltán

AU - Van Der Velden, Jolanda

AU - Stienen, Ger J M

AU - Édes, I.

AU - Papp, Z.

PY - 2008/7/1

Y1 - 2008/7/1

N2 - This study sought to characterize the relation between the oxidation of protein sulfhydryl (SH) groups and Ca2+-activated force production in the human myocardium. Triton-permeabilized left ventricular cardiomyocytes from donor hearts were exposed to an oxidative (2,2′-dithiodipyridine, DTDP) agent in vitro, and the changes in isometric force, its Ca2+ sensitivity, the cross-bridge-sensitive rate constant of force redevelopment at saturating [Ca2+] (ktr,max), and protein SH oxidation were monitored. DTDP (0.1-10 mM for 2 min) oxidized the myocardial proteins and diminished the Ca2+-activated force with different concentration dependences (EC50,SH = 0.17 ± 0.02 mM and EC 50,force = 2.46 ± 0.22 mM; mean ± SEM). The application of 2.5 mM DTDP decreased the maximal Ca2+-activated force (to 64%), its Ca2+ sensitivity (ΔpCa50 = 0.22 ± 0.02), and the steepness of the Ca2+-force relation (nHill, from 2.01 ± 0.08 to 1.76 ± 0.08). These changes were paralleled by reductions in the free SH content of the proteins (to 15%) and in k tr,max (to 75%). SH-specific labeling identified SH oxidation of myosin light chain 1 and actin at DTDP concentrations at which the changes in the contractile parameters occurred. Our data suggest that SH oxidation in selected myofilament proteins diminishes the Ca2+-activated force and its Ca2+ sensitivity through an impaired Ca2+ regulation of the actin-myosin cycle in the human heart.

AB - This study sought to characterize the relation between the oxidation of protein sulfhydryl (SH) groups and Ca2+-activated force production in the human myocardium. Triton-permeabilized left ventricular cardiomyocytes from donor hearts were exposed to an oxidative (2,2′-dithiodipyridine, DTDP) agent in vitro, and the changes in isometric force, its Ca2+ sensitivity, the cross-bridge-sensitive rate constant of force redevelopment at saturating [Ca2+] (ktr,max), and protein SH oxidation were monitored. DTDP (0.1-10 mM for 2 min) oxidized the myocardial proteins and diminished the Ca2+-activated force with different concentration dependences (EC50,SH = 0.17 ± 0.02 mM and EC 50,force = 2.46 ± 0.22 mM; mean ± SEM). The application of 2.5 mM DTDP decreased the maximal Ca2+-activated force (to 64%), its Ca2+ sensitivity (ΔpCa50 = 0.22 ± 0.02), and the steepness of the Ca2+-force relation (nHill, from 2.01 ± 0.08 to 1.76 ± 0.08). These changes were paralleled by reductions in the free SH content of the proteins (to 15%) and in k tr,max (to 75%). SH-specific labeling identified SH oxidation of myosin light chain 1 and actin at DTDP concentrations at which the changes in the contractile parameters occurred. Our data suggest that SH oxidation in selected myofilament proteins diminishes the Ca2+-activated force and its Ca2+ sensitivity through an impaired Ca2+ regulation of the actin-myosin cycle in the human heart.

UR - http://www.scopus.com/inward/record.url?scp=42949121576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42949121576&partnerID=8YFLogxK

U2 - 10.1089/ars.2007.2014

DO - 10.1089/ars.2007.2014

M3 - Article

C2 - 18331201

AN - SCOPUS:42949121576

VL - 10

SP - 1175

EP - 1184

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 7

ER -