Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This work was undertaken to provide further insights into the expression of tropism-related genes in regenerating skeletal muscle of adult rats treated with cyclosporin-A (CsA), a calcineurin inhibitor. Rats were treated with CsA for 5 days and, on the 6th day, were submitted to cryolesion of the soleus muscles. CsA treatment continued for 1, 10, and 21 days after cryolesion. Muscles were removed, frozen, and stored in liquid nitrogen. Body and muscle weights, histological sections stained with toluidine blue, and gene expression of the regeneration molecular markers, viz., desmin and neonatal myosin heavy chain, were assessed to confirm that cryolesion and CsA treatment were effective during the allowed regeneration time. Quantitative reverse transcription/polymerase chain reaction demonstrated that myostatin gene expression was not altered by either cryolesion or CsA treatment combined with cryolesion. Calpain-3 gene expression decreased at 1 day after cryolesion and also following CsA treatment combined with cryolesion. However, calpain-3 gene expression was strongly up-regulated (approximately five-fold) 10 days after cryolesion and returned to control levels at day 21. CsA treatment blocked calpain-3 gene expression rise induced by 10 days of cryolesion. Atrogin-1 gene expression was decreased at 1 day after cryolesion and following cryolesion combined with CsA treatment, returning to control levels at day 10. These results suggest that (1) calpain-3 has a differential role in the early and late stages of regeneration in a calcineurin-dependent manner, and (2) atrogin-1 is involved in the early stages of regeneration independently of calcineurin.
 ...
PMID:Expression of tropism-related genes in regenerating skeletal muscle of rats treated with cyclosporin-A. 1572 28

The calpain proteinases and their specific inhibitor calpastatin have been proposed to influence both the rates of myofibrillar protein turnover in vivo and meat tenderization postmortem. Elevated calpastatin concentrations in particular are associated with certain forms of hypertrophic growth and meat toughness. In the 5'region of the porcine calpastatin gene, there are 3 calpastatin promoters upstream of exons 1xa, 1xb, and 1u, respectively, each of which contain transcription factor-binding motifs, suggesting sensitivity to a variety of growth-promoting stimuli. This study examined the effect of the beta-adrenergic agonist clenbuterol and porcine ST (pST) treatment on calpastatin promoter usage in porcine LM in vivo using real-time PCR and also the responsiveness of transfected calpastatin promoter sequences to cyclic adenosine monophosphate (cAMP) and calcium (Ca2+)-related stimuli in reporter gene systems in cell studies. The effect of clenbuterol and pST on potential signaling pathways in vivo was also assessed by monitoring protein phosphatase 2B (calcineurin), NFATc3, calpain 3, IkappaB alpha, and NFkappaB by quantitative immunoblotting. Total calpastatin mRNA was increased by 52% (P < 0.05) after treatment with clenbuterol for 1 d and reduced by 35% (P < 0.01) after pST treatment for 7 d. Whereas clenbuterol had no significant differential effects on individual mRNA transcripts (types 1 to 3) derived from the 3 upstream promoters, pST significantly reduced all of these by 51, 39, and 40% (P < 0.001, 0.05, and 0.05), respectively. Promoter activity was increased in rat L6G8 cells transfected with a construct derived from exon 1u after treatment with dibutyryl cAMP (68%, P < 0.05) or forskolin (43%, P < 0.05), whereas 1xa activity was reduced by both of these agents (47 and 33%, respectively, P < 0.05). Treatment of cells with the calcium ionophore calcimycin reduced the activity of the 1u promoter by 40% (P < 0.01), with no effect on the other promoter constructs. Cyclosporin A had no effect on any promoter construct. The only signaling pathway component to be significantly altered by the in vivo treatments was calcineurin, which was decreased by 24% (P < 0.05) in clenbuterol-treated animals. In conclusion, 2 types of growth promoter in pigs had contrasting effects on calpastatin expression in LM. Transfected calpastatin promoters were differentially sensitive to cAMP- and Ca2+-related stimuli, in agreement with the proposed mode of action of the 2 growth promoters.
 ...
PMID:Effect of anabolic agents on calpastatin promoters in porcine skeletal muscle and their responsiveness to cyclic adenosine monophosphate- and calcium-related stimuli. 1703 91