Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysosomal cysteine proteinase (cathepsin B, H, and L) and MMP-7ase muscle metalloproteinase activities were measured in serum from Duchenne muscular dystrophic male patients and their mothers as gene-carriers. The activity of cathepsin H significantly increased in the Duchenne muscular dystrophic (DMD)-hemizygotes group and in the group of DMD heterozygotes. Significant positive correlation was found between the activity of serum creatine kinase (which previously has been proven to be a marker of muscular dystrophy) and of cathepsin L in the DMD-hemizygotes group. Furthermore, correlations were found between the activity of creatine kinase and MMP-7ase or between activity of creatine kinase and cathepsin H in the DMD heterozygotes. The changes in activity of proteolytic enzymes in serum of dystrophic patients can be explained by the elevated proteolytic enzyme activity in dystrophic muscle observed previously.
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PMID:Cysteine and metalloproteinase activities in serum of Duchenne muscular dystrophic genotypes. 320 67

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.
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PMID:Down-regulation of genes in the lysosomal and ubiquitin-proteasome proteolytic pathways in calpain-3-deficient muscle. 1267 59

The overexpression of the cysteine protease calpain is associated with many diseases, including brain trauma, spinal cord injury, Alzheimer's disease, Parkinson's disease, muscular dystrophy, arthritis, and cataract. Calpastatin is the naturally occurring specific regulator of calpain activity. It has previously been reported that a 20-mer peptide truncated from region B of calpastatin inhibitory domain 1 (named CP1B) retains both the affinity and selectivity of calpastatin toward calpain, exhibiting a K(i) of 26 nM against mu-calpain, and is 1000-fold more selective for mu-calpain than cathepsin L. Both the wild-type and beta-Ala mutant CP1B peptides exhibit a propensity to adopt a looplike conformation between Glu10 and Lys13. A computational study of human wild-type CP1B and the beta-Ala mutants of this peptide was conducted. The resulting structural predictions were compared with the crystal structure of the calpain-calpastatin complex and were correlated with experimental IC(50) values. These findings suggest that the conformational preference of the loop region between Glu10 and Lys13 of CP1B in the absence of calpain may contribute to the inhibitory activity of this series of peptides against calpain.
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PMID:Molecular modeling studies of peptide inhibitors highlight the importance of conformational prearrangement for inhibition of calpain. 2049 28