Comparative decline of the protein profiles of nebulin in response to denervation in skeletal muscle

Jih Hua Wei, Nen Chung Chang, Sy Ping Chen, Pitchairaj Geraldine, Thanasekaran Jayakumar, Tsorng Harn Fong

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The sliding filament model of the sarcomere was developed more than half a century ago. This model, consisting only of thin and thick filaments, has been efficacious in elucidating many, but not all, features of skeletal muscle. Work during the 1980s revealed the existence of two additional filaments: the giant filamentous proteins titin and nebulin. Nebulin, a giant myofibrillar protein, acts as a protein ruler to maintain the lattice arrays of thin filaments and plays a role in signal transduction and contractile regulation. However, the change of nebulin and its effect on thin filaments in denervation-induced atrophic muscle remains unclear. The purpose of this study is to examine the content and pattern of nebulin, myosin heavy chain (MHC), actin, and titin in innervated and denervated tibialis anterior (TA) muscles of rats using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), densitometry and electron microscopic (EM) analyses. The results revealed that denervation induced muscle atrophy is accompanied by decreased nebulin content in a time-dependent manner. For instant, the levels of nebulin in denervated muscles were markedly (P <0.05) decreased, about 24.6% and 40.2% in comparison with innervated muscle after denervation of 28 and 56 days, respectively. The nebulin/MHC, nebulin/actin, and nebulin/titin ratios were decreased, suggesting a concomitant reduction of nebulin in denervated muscle. Moreover, a western blotting assay proved that nebulin declined faster than titin on 28 and 56 days of denervated muscle. In addition, EM study revealed that the disturbed arrangements of myofilaments and a disorganized contractile apparatus were also observed in denervated muscle. Overall, the present study provides evidence that nebulin is more sensitive to the effect of denervation than MHC, actin, and titin. Nebulin decline indeed resulted in disintegrate of thin filaments and shortening of sarcomeres.

Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume466
Issue number1
DOIs
Publication statusPublished - Aug 6 2015

Fingerprint

Denervation
Muscle
Skeletal Muscle
Connectin
Proteins
Muscles
Myosin Heavy Chains
Actins
Sarcomeres
nebulin
Muscle Denervation
Electrons
Signal transduction
Muscular Atrophy
Densitometry
Myofibrils
Electrophoresis
Sodium Dodecyl Sulfate
Rats
Polyacrylamide Gel Electrophoresis

Keywords

  • Denervation
  • Electron microscopy
  • Muscle atrophy
  • Myofibrillar protein
  • Nebulin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Comparative decline of the protein profiles of nebulin in response to denervation in skeletal muscle. / Wei, Jih Hua; Chang, Nen Chung; Chen, Sy Ping; Geraldine, Pitchairaj; Jayakumar, Thanasekaran; Fong, Tsorng Harn.

In: Biochemical and Biophysical Research Communications, Vol. 466, No. 1, 06.08.2015, p. 95-102.

Research output: Contribution to journalArticle

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abstract = "The sliding filament model of the sarcomere was developed more than half a century ago. This model, consisting only of thin and thick filaments, has been efficacious in elucidating many, but not all, features of skeletal muscle. Work during the 1980s revealed the existence of two additional filaments: the giant filamentous proteins titin and nebulin. Nebulin, a giant myofibrillar protein, acts as a protein ruler to maintain the lattice arrays of thin filaments and plays a role in signal transduction and contractile regulation. However, the change of nebulin and its effect on thin filaments in denervation-induced atrophic muscle remains unclear. The purpose of this study is to examine the content and pattern of nebulin, myosin heavy chain (MHC), actin, and titin in innervated and denervated tibialis anterior (TA) muscles of rats using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), densitometry and electron microscopic (EM) analyses. The results revealed that denervation induced muscle atrophy is accompanied by decreased nebulin content in a time-dependent manner. For instant, the levels of nebulin in denervated muscles were markedly (P <0.05) decreased, about 24.6{\%} and 40.2{\%} in comparison with innervated muscle after denervation of 28 and 56 days, respectively. The nebulin/MHC, nebulin/actin, and nebulin/titin ratios were decreased, suggesting a concomitant reduction of nebulin in denervated muscle. Moreover, a western blotting assay proved that nebulin declined faster than titin on 28 and 56 days of denervated muscle. In addition, EM study revealed that the disturbed arrangements of myofilaments and a disorganized contractile apparatus were also observed in denervated muscle. Overall, the present study provides evidence that nebulin is more sensitive to the effect of denervation than MHC, actin, and titin. Nebulin decline indeed resulted in disintegrate of thin filaments and shortening of sarcomeres.",
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AU - Jayakumar, Thanasekaran

AU - Fong, Tsorng Harn

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