Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.54 (calpain 3)
 430 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We hypothesized that estrogen administration would attenuate skeletal muscle neutrophil infiltration, indices of muscle membrane disruption, and muscle calpain activity shortly after the termination of exercise. Ovariectomized female rats were implanted with either an estogen pellet (25 mg beta-estradiol) or a placebo pellet. Two weeks postimplant, animals were killed either at rest or 1 h after running exercise (60 min at 21 m x min(-1), 12% grade). The 4 experimental groups (n = 12) used were: unexercised placebo (UP), unexercised estrogen (UE), exercised placebo (EP), and exercised estrogen (EE). Blood samples were analyzed for creatine kinase (CK) activity and estradiol content. Plantaris and gastrocnemius muscles were removed and histochemical determination of neutrophil content or biochemical determination of myeloperoxidase (MPO), glucose-6-phosphate dehydrogenase (G6PD), and calpain-like activity determined. Estrogen supplemented animals had 10-20-fold higher circulating estradiol levels than placebo animals. EP animals had significantly higher (P < 0.05) circulating CK activities than EE or unexercised animals. Muscle neutrophil concentrations were significantly (P < 0.01) elevated in EP and EE groups compared with unexercised controls, with EP muscle neutrophil levels also being over 60% greater (P < 0.05) than in EE animals. EP animals also had higher (P < 0.05) muscle MPO activities than unexercised or EE animals. Muscle G6PD activities were not significantly different between any groups. Muscle caplain-like activities were 80% higher (P < 0.01) in EP animals than EE animals with calpain-like activities in EE animals similar to unexercised groups. These results indicate that estrogen supplementation in ovariectomized rats attenuated 1-h post-exercise serum CK activities, muscle neutrophil infiltration, MPO activities, and calpain-like activities when compared with exercised, unsupplemented animals. This supports the possibility of a relationship between estrogen, calpain dependent production of neutrophil chemo-attractant peptides, and 1-h post-exercise skeletal muscle neutrophil infiltration.
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PMID:Estrogen effect on post-exercise skeletal muscle neutrophil infiltration and calpain activity. 1140 43

We report the clinical and genetic analysis of a 63-year-old man with progressive weakness developing over more than 20 years. Prior to his initial visit, he underwent multiple neurological and rheumatological evaluations and was treated for possible inflammatory myopathy. He did not respond to any treatment that was prescribed and was referred to our center for another opinion. He underwent a neurological evaluation, electromyography, magnetic resonance imaging of his legs, and a muscle biopsy. All testing indicated a chronic myopathy without inflammatory features suggesting a genetic myopathy. Whole-exome sequencing testing more than 50 genes known to cause myopathy revealed variants in the COL6A3 (rs144651558), RYR1 (rs143445685), CAPN3 (rs138172448), and DES (rs144901249) genes. We hypothesized that the inheritance pattern could follow a digenic pattern of inheritance. Screening for these polymorphisms in an unaffected sister revealed the presence of all these same variants except for that in the CAPN3 gene. All variants were studied to determine their frequency and if they had been previously reported as mutations. They were also subjected to protein modeling programs, including SIFT, PolyPhen, and MutationTaster. This analysis indicated that the CAPN3 variant c.1663G>A (rs138172448), which results in a p.Val555Ile change, and the DES gene variant c.656C>T (rs144901249), which results in a p.Thr219Ile change, are both predicted to be damaging. These 2 variants were further investigated employing the STRING program that analyzes protein networks and pathways. This analysis provided further support for our hypothesis that these mutations in the CAPN3 and DES genes, through digenic inheritance, are the cause of the myopathy in this patient.
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PMID:Limb Girdle Muscular Dystrophy due to Digenic Inheritance of DES and CAPN3 Mutations. 3032 56