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Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres

Heme released from red blood cells targets a number of cell components including the cytoskeleton. The purpose of the present study was to determine the impact of free heme (20–300 µM) on human skeletal muscle fibres made available during orthopedic surgery. Isometric force production and oxidative...

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Autores principales: Alvarado, Gerardo, Tóth, Attila, Csősz, Éva, Kalló, Gergő, Dankó, Katalin, Csernátony, Zoltán, Smith, Ann, Gram, Magnus, Akerström, Bo, Édes, István, Balla, György, Papp, Zoltán, Balla, József
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663642/
https://www.ncbi.nlm.nih.gov/pubmed/33142923
http://dx.doi.org/10.3390/ijms21218172
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author Alvarado, Gerardo
Tóth, Attila
Csősz, Éva
Kalló, Gergő
Dankó, Katalin
Csernátony, Zoltán
Smith, Ann
Gram, Magnus
Akerström, Bo
Édes, István
Balla, György
Papp, Zoltán
Balla, József
author_facet Alvarado, Gerardo
Tóth, Attila
Csősz, Éva
Kalló, Gergő
Dankó, Katalin
Csernátony, Zoltán
Smith, Ann
Gram, Magnus
Akerström, Bo
Édes, István
Balla, György
Papp, Zoltán
Balla, József
author_sort Alvarado, Gerardo
collection PubMed
description Heme released from red blood cells targets a number of cell components including the cytoskeleton. The purpose of the present study was to determine the impact of free heme (20–300 µM) on human skeletal muscle fibres made available during orthopedic surgery. Isometric force production and oxidative protein modifications were monitored in permeabilized skeletal muscle fibre segments. A single heme exposure (20 µM) to muscle fibres decreased Ca(2+)-activated maximal (active) force (F(o)) by about 50% and evoked an approximately 3-fold increase in Ca(2+)-independent (passive) force (F(passive)). Oxidation of sulfhydryl (SH) groups was detected in structural proteins (e.g., nebulin, α-actinin, meromyosin 2) and in contractile proteins (e.g., myosin heavy chain and myosin-binding protein C) as well as in titin in the presence of 300 µM heme. This SH oxidation was not reversed by dithiothreitol (50 mM). Sulfenic acid (SOH) formation was also detected in the structural proteins (nebulin, α-actinin, meromyosin). Heme effects on SH oxidation and SOH formation were prevented by hemopexin (Hpx) and α1-microglobulin (A1M). These data suggest that free heme has a significant impact on human skeletal muscle fibres, whereby oxidative alterations in structural and contractile proteins limit contractile function. This may explain and or contribute to the weakness and increase of skeletal muscle stiffness in chronic heart failure, rhabdomyolysis, and other hemolytic diseases. Therefore, therapeutic use of Hpx and A1M supplementation might be effective in preventing heme-induced skeletal muscle alterations.
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spelling pubmed-76636422020-11-14 Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres Alvarado, Gerardo Tóth, Attila Csősz, Éva Kalló, Gergő Dankó, Katalin Csernátony, Zoltán Smith, Ann Gram, Magnus Akerström, Bo Édes, István Balla, György Papp, Zoltán Balla, József Int J Mol Sci Article Heme released from red blood cells targets a number of cell components including the cytoskeleton. The purpose of the present study was to determine the impact of free heme (20–300 µM) on human skeletal muscle fibres made available during orthopedic surgery. Isometric force production and oxidative protein modifications were monitored in permeabilized skeletal muscle fibre segments. A single heme exposure (20 µM) to muscle fibres decreased Ca(2+)-activated maximal (active) force (F(o)) by about 50% and evoked an approximately 3-fold increase in Ca(2+)-independent (passive) force (F(passive)). Oxidation of sulfhydryl (SH) groups was detected in structural proteins (e.g., nebulin, α-actinin, meromyosin 2) and in contractile proteins (e.g., myosin heavy chain and myosin-binding protein C) as well as in titin in the presence of 300 µM heme. This SH oxidation was not reversed by dithiothreitol (50 mM). Sulfenic acid (SOH) formation was also detected in the structural proteins (nebulin, α-actinin, meromyosin). Heme effects on SH oxidation and SOH formation were prevented by hemopexin (Hpx) and α1-microglobulin (A1M). These data suggest that free heme has a significant impact on human skeletal muscle fibres, whereby oxidative alterations in structural and contractile proteins limit contractile function. This may explain and or contribute to the weakness and increase of skeletal muscle stiffness in chronic heart failure, rhabdomyolysis, and other hemolytic diseases. Therefore, therapeutic use of Hpx and A1M supplementation might be effective in preventing heme-induced skeletal muscle alterations. MDPI 2020-10-31 /pmc/articles/PMC7663642/ /pubmed/33142923 http://dx.doi.org/10.3390/ijms21218172 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alvarado, Gerardo
Tóth, Attila
Csősz, Éva
Kalló, Gergő
Dankó, Katalin
Csernátony, Zoltán
Smith, Ann
Gram, Magnus
Akerström, Bo
Édes, István
Balla, György
Papp, Zoltán
Balla, József
Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres
title Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres
title_full Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres
title_fullStr Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres
title_full_unstemmed Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres
title_short Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres
title_sort heme-induced oxidation of cysteine groups of myofilament proteins leads to contractile dysfunction of permeabilized human skeletal muscle fibres
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663642/
https://www.ncbi.nlm.nih.gov/pubmed/33142923
http://dx.doi.org/10.3390/ijms21218172
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