The investigated intronic CAPN3 variant NM_000070.3:c.1746-20C>G occurs in the Central and Eastern Europe with a frequency of >1% and there are conflicting interpretations on its pathogenicity. We collected data on 14 patients carrying the CAPN3 c.1746-20C>G variant in trans position with another CAPN3 pathogenic/likely pathogenic variant. The patients compound heterozygous for the CAPN3 c.1746-20C>G variant presented a phenotype consistent with calpainopathy of mild/medium severity. This variant is most frequent in the North/West regions of Russia and may originate from that area. Molecular studies revealed that different splicing isoforms are produced in the muscle. We hypothesize that c.1746-20C>G is a hypomorphic variant with a reduction of RNA and protein expression and only individuals having a higher ratio of abnormal isoforms are affected. Reclassification of the CAPN3 variant c.1746-20C>G from variant with a conflicting interpretation of pathogenicity to hypomorphic variant explains many unidentified cases of limb girdle muscular dystrophy R1 calpain 3-related in Eastern and Central Europe.

• MeSH
• kalpain * genetika   MeSH
• lidé MeSH
• mutace MeSH
• pletencové svalové dystrofie * genetika   MeSH
• sestřih RNA MeSH
• svalové proteiny * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Bcl-2/E1B-19K-interacting protein 3 (BNIP3) is a member of the apoptotic B-cell lymphoma-2 family that regulates cell death. Although BNIP3 targeted normally to the mitochondrial outer membrane by its transmembrane domain was originally considered to be essential for its pro-apoptotic activity, accumulating evidence has shown that BNIP3 is localized to endoplasmic reticulum at physiological conditions and that forced expression of BNIP3 can initiate cell death via multiple pathways depending on the subcellular compartment it targets. Targeting BNIP3 to endoplasmic reticulum has been shown to participate in cell death during endoplasmic reticulum stress. However, the molecular events responsible for BNIP3-induced cell death in the endoplasmic reticulum remain poorly understood. In the present study, the transmembrane domain of BNIP3 was replaced with a segment of cytochrome b5 that targets BNIP3 into endoplasmic reticulum, which induced cell death as effectively as its wild-type molecule in the SW480 cell line (colon carcinoma). Furthermore, a pan-caspase inhibitor, z-VAD-fmk, and PD150606, a specific calpain inhibitor, both significantly suppressed the endoplasmic reticulum-targeted BNIP3-induced cell death. These results suggest that endoplasmic reticulum-targeted BNIP3 induced a mixed mode of cell death requiring both caspases and calpains.

• MeSH
• apoptóza MeSH
• buněčná smrt * MeSH
• endoplazmatické retikulum * metabolismus   MeSH
• kalpain * MeSH
• kaspasy * MeSH
• lidé MeSH
• membránové proteiny MeSH
• protoonkogenní proteiny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• epidermis * účinky záření   metabolismus   MeSH
• kalpain * metabolismus   antagonisté a inhibitory   MeSH
• keratinocyty účinky záření   metabolismus   MeSH
• lidé MeSH
• škára účinky záření   patologie   metabolismus   cytologie   MeSH
• ultrafialové záření * škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• dopisy MeSH

• MeSH
• finanční podpora výzkumu jako téma MeSH
• kalpain metabolismus   MeSH
• kultivované buňky MeSH
• ledviny metabolismus   účinky léků   MeSH
• lidé MeSH
• neurony metabolismus   MeSH
• transportní systémy pro neutrální aminokyseliny genetika   chemie   metabolismus   MeSH
• vápník farmakologie   metabolismus   MeSH
• vazebná místa genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

We conducted pooled and meta-analyses of the association of the calpain-10 gene (CAPN10) polymorphisms SNP-43, Indel-19 and SNP-63 individually and as haplotypes with type 2 diabetes (T2D) in 3237 patients and 2935 controls of European ancestry. In the pooled analyses, the common SNP-43*G allele was associated with modest but statistically significant increased risk of T2D (odds ratio (OR)=1.11 (95% confidence interval (CI), 1.02-1.20), P=0.01). Two haplotype combinations were associated with increased risk of T2D (1-2-1/1-2-1, OR=1.20 (1.03-1.41), P=0.02; and 1-1-2/1-2-1, OR=1.26 (1.01-1.59), P=0.04) and one with decreased risk (1-1-1/2-2-1, OR=0.86 (0.75-0.99), P=0.03). The meta-analysis also showed a significant effect of the 1-2-1/1-2-1 haplogenotype on risk (OR=1.25 (1.05-1.50), P=0.01). However, there was evidence for heterogeneity with respect to this effect (P=0.06). The heterogeneity appeared to be due to data sets in which the cases were selected from samples used in linkage studies of T2D. Using only the population-based case-control samples removed the heterogeneity (P=0.89) and strengthened the evidence for association with T2D in both the pooled (SNP-43*G, OR=1.19 (1.07-1.32), P=0.001; 1-2-1/1-2-1 haplogenotype, OR=1.46 (1.19-1.78), P=0.0003; 1-1-2/1-2-1 haplogenotype, OR=1.52 (1.12-2.06), P=0.007; and 1-1-1/2-2-1 haplogenotype, OR=0.83 (0.70-0.99), P=0.03) and the meta-analysis (SNP-43*G, OR=1.18 (1.05-1.32), P=0.005; 1-2-1/1-2-1 haplogenotype, OR=1.68 (1.33-2.11), P=0.00001). The pooled and meta-analyses as well as the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of T2D in Europeans.

• MeSH
• běloši * genetika   MeSH
• diabetes mellitus 2. typu * genetika   MeSH
• haplotypy genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• kalpain * genetika   MeSH
• lidé MeSH
• vazebná nerovnováha * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• metaanalýza MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• finanční podpora výzkumu jako téma MeSH
• ischemická choroba srdeční MeSH
• kalpain farmakologie   MeSH
• kontrakce myokardu účinky záření   MeSH
• krysa rodu rattus MeSH
• myofibrily fyziologie   MeSH
• proteiny analýza   MeSH
• reperfuze myokardu MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

Skeletal muscle atrophy is associated with a loss of muscle protein which may result from both increased proteolysis and decreased protein synthesis. Investigations on cell signaling pathways that regulate muscle atrophy have promoted our understanding of this complicated process. Emerging evidence implicates that calpains play key roles in dysregulation of proteolysis seen in muscle atrophy. Moreover, studies have also shown that abnormally activated calpain results muscle atrophy via its downstream effects on ubiquitin-proteasome pathway (UPP) and Akt phosphorylation. This review will discuss the role of calpains in regulation of skeletal muscle atrophy mainly focusing on its collaboration with either UPP or Akt in atrophy conditions in hope to stimulate the interest in development of novel therapeutic interventions for skeletal muscle atrophy.

• MeSH
• hypertrofie MeSH
• interakce mezi receptory a ligandy MeSH
• kalpain metabolismus   MeSH
• lidé MeSH
• proteasomový endopeptidasový komplex metabolismus   MeSH
• proteolýza * MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• signální transdukce MeSH
• svalová atrofie metabolismus   MeSH
• svalové proteiny metabolismus   MeSH
• ubikvitin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Leták informuje o pletencové svalové dystrofii LGMD2A (deficit calpainu 3) a obsahuje mapku České republiky se seznamem neuromuskulárních center.

• MeSH
• kalpain MeSH
• patologie MeSH
• Publikační typ
• letáky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• patologie

• Publikační typ
• abstrakt z konference MeSH

• MeSH
• cytoplazma MeSH
• kalpain MeSH
• signální transdukce MeSH