Denervation-induced activation of the standard proteasome and immunoproteasome

Haiming M. Liu, Deborah A. Ferrington, Cory W. Baumann, Ladora V. Thompson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The standard 26S proteasome is responsible for the majority of myofibrillar protein degradation leading to muscle atrophy. The immunoproteasome is an inducible form of the proteasome. While its function has been linked to conditions of atrophy, its contribution to muscle proteolysis remains unclear. Therefore, the purpose of this study was to determine if the immunoproteasome plays a role in skeletal muscle atrophy induced by denervation. Adult male C57BL/6 wild type (WT) and immunoproteasome knockout lmp7-/-/mecl-1-/- (L7M1) mice underwent tibial nerve transection on the left hindlimb for either 7 or 14 days, while control mice did not undergo surgery. Proteasome activity (caspase-, chymotrypsin-, and trypsin-like), protein content of standard proteasome (β1, β5 and β2) and immunoproteasome (LMP2, LMP7 and MECL-1) catalytic subunits were determined in the gastrocnemius muscle. Denervation induced significant atrophy and was accompanied by increased activities and protein content of the catalytic subunits in both WT and L7M1 mice. Although denervation resulted in a similar degree of muscle atrophy between strains, the mice lacking two immunoproteasome subunits showed a differential response in the extent and duration of proteasome features, including activities and content of the β1, β5 and LMP2 catalytic subunits. The results indicate that immunoproteasome deficiency alters the proteasome's composition and activities. However, the immunoproteasome does not appear to be essential for muscle atrophy induced by denervation.

Original languageEnglish (US)
Article numbere0166831
JournalPloS one
Volume11
Issue number11
DOIs
StatePublished - Nov 2016

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proteasome endopeptidase complex
Denervation
Proteasome Endopeptidase Complex
Muscular Atrophy
Muscle
muscular atrophy
Chemical activation
protein subunits
Catalytic Domain
mice
Proteolysis
Atrophy
atrophy
Skeletal Muscle
Tibial Nerve
protein content
Hindlimb
muscles
Caspases
Proteins

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Denervation-induced activation of the standard proteasome and immunoproteasome. / Liu, Haiming M.; Ferrington, Deborah A.; Baumann, Cory W.; Thompson, Ladora V.

In: PloS one, Vol. 11, No. 11, e0166831, 11.2016.

Research output: Contribution to journalArticle

Liu, Haiming M. ; Ferrington, Deborah A. ; Baumann, Cory W. ; Thompson, Ladora V. / Denervation-induced activation of the standard proteasome and immunoproteasome. In: PloS one. 2016 ; Vol. 11, No. 11.
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