| First Author | Combaret L | Year | 2003 |
| Journal | Int J Biochem Cell Biol | Volume | 35 |
| Issue | 5 | Pages | 676-84 |
| PubMed ID | 12672459 | Mgi Jnum | J:102531 |
| Mgi Id | MGI:3607730 | Doi | 10.1016/s1357-2725(02)00357-6 |
| Citation | Combaret L, et al. (2003) Down-regulation of genes in the lysosomal and ubiquitin-proteasome proteolytic pathways in calpain-3-deficient muscle. Int J Biochem Cell Biol 35(5):676-84 |
| abstractText | Calpain-3 deficiency leads to muscular dystrophy in humans and mice and to perturbation of the NFkappaB/IkappaB 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 approximately 47% (P<0.005) in the gastrocnemius muscle from calpain-3 deficient mice. In contrast, muscle mRNA levels for ubiquitin and subunit S5a of the 26S proteasome were unaffected by calpain-3 deficiency. Taken together these data demonstrate that the expression of some genes that are involved in distinct proteolytic pathways is selectively and coordinately down-regulated without any effect on proteolysis. This suggests new pathophysiological hypotheses, e.g. a lack of maturation of NFkappaB precursor and/or a defect in specific substrate targeting. |
