Down-regulation of genes in the lysosomal and ubiquitin-proteasome proteolytic pathways in calpain-3-deficient muscle

• Published in: The international journal of biochemistry & cell biology 2003-05, Vol.35 (5), p.676-684
• Main Authors: Combaret, Lydie, Béchet, Daniel, Claustre, Agnès, Taillandier, Daniel, Richard, Isabelle, Attaix, Didier
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Northern; Calpain - deficiency; Calpain - genetics; Calpain-3; Cathepsin B - metabolism; Cathepsin L; Cathepsins; Cathepsins - metabolism; Cysteine Endopeptidases - metabolism; Down-Regulation; Life Sciences; Lysosomes - metabolism; Mice; Mice, Knockout; Multienzyme Complexes - metabolism; Muscle Proteins; Muscle, Skeletal - metabolism; Muscular Dystrophies - genetics; Muscular Dystrophies - metabolism; Peptide Fragments - deficiency; Peptide Fragments - genetics; Peptide Hydrolases - metabolism; Proteasome Endopeptidase Complex; Protein breakdown; Skeletal muscle; Ubiquitin - metabolism; Ubiquitin-proteasome system
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/S1357-2725(02)00357-6

Calpain-3 deficiency leads to muscular dystrophy in humans and mice and to perturbation of the NFκB/IκB pathway. As this phenotype is mainly atrophic, this study was performed to determine whether protein turnover and/or proteolytic gene expression was altered in muscles following calpain-3 deficiency. In vitro rates of protein turnover and of substrate ubiquitination, cathepsin B and B+L activities, and mRNA levels for several proteolytic genes were measured in skeletal muscles from 4–5 month-old control and calpain-3 knockout mice. Rates of protein synthesis and breakdown, cathepsin activities, and rates of substrate ubiquitination remained stable in muscles from calpain-3 deficient mice. However, and surprisingly, mRNA levels for cathepsin L, the 14-kDa ubiquitin-conjugating enzyme E2, and the C2 subunit of the 20S proteasome decreased by ∼47% ( P