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- Alvarado, GerardoUniversity of Debrecen (author)
Heme-induced oxidation of cysteine groups of myofilament proteins leads to contractile dysfunction of permeabilized human skeletal muscle fibres
- Article/chapterEnglish2020
Publisher, publication year, extent ...
- 2020-10-31
- MDPI AG,2020
- 19 s.
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- LIBRIS-ID:oai:lup.lub.lu.se:9f997d3e-5128-4193-8716-70e1101dcd8a
- https://lup.lub.lu.se/record/9f997d3e-5128-4193-8716-70e1101dcd8aURI
- https://doi.org/10.3390/ijms21218172DOI
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- Language:English
- Summary in:English
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- Background: 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. Methods: Isometric force production and oxidative protein modifications were monitored in permeabilized skeletal muscle fibre segments. Results: A single heme exposure (20 µM) to muscle fibres decreased Ca2+-activated maximal (active) force (Fo) by about 50% and evoked an approximately 3-fold increase in Ca2+-independent (passive) force (Fpassive). 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). Conclusions: 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.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
- Chronic heart failure
- Contractile dysfunction
- Heme
- Hemopexin
- Oxidation
- Skeletal muscle fibre
- Skeletal muscle myopathy
- Sulfenic acid formation
- Sulfhydryl groups
- α1-microglobulin
Added entries (persons, corporate bodies, meetings, titles ...)
- Tóth, AttilaUniversity of Debrecen (author)
- Csősz, ÉvaUniversity of Debrecen (author)
- Kalló, GergőUniversity of Debrecen (author)
- Dankó, KatalinUniversity of Debrecen (author)
- Csernátony, ZoltánUniversity of Debrecen (author)
- Smith, AnnUniversity of Missouri-Kansas City (author)
- Gram, MagnusLund University,Lunds universitet,Neonatologi,Forskargrupper vid Lunds universitet,Neonatology,Lund University Research Groups(Swepub:lu)medk-mo0 (author)
- Akerström, BoLund University,Lunds universitet,Antioxidationsmedicin,Forskargrupper vid Lunds universitet,Antioxidation medicine,Lund University Research Groups(Swepub:lu)medk-bak (author)
- Édes, IstvánUniversity of Debrecen (author)
- Balla, GyörgyUniversity of Debrecen (author)
- Papp, ZoltánUniversity of Debrecen (author)
- Balla, JózsefUniversity of Debrecen (author)
- University of DebrecenUniversity of Missouri-Kansas City (creator_code:org_t)
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- In:International Journal of Molecular Sciences: MDPI AG21:211661-65961422-0067
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