Increasing myosin light chain 3f (MLC3f) protects against a decline in contractile velocity

Jong Hee Kim, Theodore Graber, Haiming Liu, Atsushi Asakura, La Dora V. Thompson

Research output: Contribution to journalArticle

Abstract

Disuse induces adaptations in skeletal muscle, which lead to muscle deterioration. Hindlimb-unloading (HU) is a well-established model to investigate cellular mechanisms responsible for disuse-induced skeletal muscle dysfunction. In myosin heavy chain (MHC) type IIB fibers HU induces a reduction in contraction speed (Vo) and a reduction in the relative myosin light chain 3f (MLC3f) protein content compared with myosin light chain 1f (MLC1f) protein. This study tested the hypothesis that increasing the relative MLC3f protein content via rAd-MLC3f vector delivery would attenuate the HU-induced decline in Vo in single MHC type IIB fibers. Fischer-344 rats were randomly assigned to one of three groups: control, HU for 7 days, and HU for 7 days plus rAd-MLC3f. The semimembranosus muscles were injected with rAd-MLC3f (3.75 x 10 11 –5 x 10 11 ifu/ml) at four days after the initiation of HU. In single MHC type IIB fibers the relative MLC3f content decreased by 25% (12.00 ±0.60% to 9.06±0.66%) and Vo was reduced by 29% (3.22±0.14fl/s vs. 2.27±0.08fl/s) with HU compared to the control group. The rAd-MLC3f injection resulted in an increase in the relative MLC3f content (12.26±1.19%) and a concomitant increase in Vo (2.90±0.15fl/s) of MHC type IIB fibers. A positive relationship was observed between the percent of MLC3f content and Vo. Maximal isometric force and specific tension were reduced with HU by 49% (741.45±44.24μN to 379.09±23.77μN) and 33% (97.58±4.25kN/m 2 to 65.05±2.71kN/m 2 ), respectively compared to the control group. The rAd-MLC3f injection did not change the HU-induced decline in force or specific tension. Collectively, these results indicate that rAd-MLC3f injection rescues hindlimb unloading-induced decline in Vo in MHC type IIB single muscle fibers.

Original languageEnglish (US)
Article numbere0214982
JournalPloS one
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2019

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myosin light chains
Myosin Light Chains
Hindlimb Suspension
Unloading
Myosin Heavy Chains
myosin heavy chains
Muscle
Fibers
injection
Muscles
Control Groups
Injections
skeletal muscle
Skeletal Muscle
protein content
hindlimbs
muscles
Proteins
Inbred F344 Rats
muscle fibers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kim, J. H., Graber, T., Liu, H., Asakura, A., & Thompson, L. D. V. (2019). Increasing myosin light chain 3f (MLC3f) protects against a decline in contractile velocity. PloS one, 14(4), [e0214982]. https://doi.org/10.1371/journal.pone.0214982

Increasing myosin light chain 3f (MLC3f) protects against a decline in contractile velocity. / Kim, Jong Hee; Graber, Theodore; Liu, Haiming; Asakura, Atsushi; Thompson, La Dora V.

In: PloS one, Vol. 14, No. 4, e0214982, 01.04.2019.

Research output: Contribution to journalArticle

Kim, Jong Hee ; Graber, Theodore ; Liu, Haiming ; Asakura, Atsushi ; Thompson, La Dora V. / Increasing myosin light chain 3f (MLC3f) protects against a decline in contractile velocity. In: PloS one. 2019 ; Vol. 14, No. 4.
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abstract = "Disuse induces adaptations in skeletal muscle, which lead to muscle deterioration. Hindlimb-unloading (HU) is a well-established model to investigate cellular mechanisms responsible for disuse-induced skeletal muscle dysfunction. In myosin heavy chain (MHC) type IIB fibers HU induces a reduction in contraction speed (Vo) and a reduction in the relative myosin light chain 3f (MLC3f) protein content compared with myosin light chain 1f (MLC1f) protein. This study tested the hypothesis that increasing the relative MLC3f protein content via rAd-MLC3f vector delivery would attenuate the HU-induced decline in Vo in single MHC type IIB fibers. Fischer-344 rats were randomly assigned to one of three groups: control, HU for 7 days, and HU for 7 days plus rAd-MLC3f. The semimembranosus muscles were injected with rAd-MLC3f (3.75 x 10 11 –5 x 10 11 ifu/ml) at four days after the initiation of HU. In single MHC type IIB fibers the relative MLC3f content decreased by 25{\%} (12.00 ±0.60{\%} to 9.06±0.66{\%}) and Vo was reduced by 29{\%} (3.22±0.14fl/s vs. 2.27±0.08fl/s) with HU compared to the control group. The rAd-MLC3f injection resulted in an increase in the relative MLC3f content (12.26±1.19{\%}) and a concomitant increase in Vo (2.90±0.15fl/s) of MHC type IIB fibers. A positive relationship was observed between the percent of MLC3f content and Vo. Maximal isometric force and specific tension were reduced with HU by 49{\%} (741.45±44.24μN to 379.09±23.77μN) and 33{\%} (97.58±4.25kN/m 2 to 65.05±2.71kN/m 2 ), respectively compared to the control group. The rAd-MLC3f injection did not change the HU-induced decline in force or specific tension. Collectively, these results indicate that rAd-MLC3f injection rescues hindlimb unloading-induced decline in Vo in MHC type IIB single muscle fibers.",
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