Effect of cyclosporin A treatment on the in vivo regulation of type I MHC gene expression

Journal of Applied Physiology
Julia M GigerKenneth M Baldwin

Abstract

Rat soleus muscle consists predominantly of slow type I fibers. We have shown previously through deletion analysis that the highest level of reporter activity that we measure when injecting type I myosin heavy chain (MHC) promoter (MHC(1))-linked luciferase plasmid into soleus muscles depends on the presence of a 550-bp upstream enhancer (3,450-2,900) region of the promoter. Because the calcineurin-nuclear factor of activated T cells (NFAT) pathway has been implicated in the regulation of the slow muscle gene program, particularly the MHC(1) isoform, and the MHC(1) promoter contains several putative NFAT sites, we examined via deletion and mutation analyses whether this pathway is involved in the regulation of promoter activity in soleus. Nine days of treatment with the calcineurin inhibitor cyclosporin A (CsA) caused a significant decrease in activity of the -3,500- and -3,450-bp promoters compared with vehicle-treated rats. Truncation of the promoter to -2,900 bp or smaller reduced the activity and also eliminated the CsA responsiveness, thus implying that the enhancer region is required for CsA responsiveness. Surprisingly, mutating the two NFAT elements within the enhancer region had no obvious effect on promoter activity. ...Continue Reading

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Citations

Jan 27, 2006·Pflügers Archiv : European journal of physiology·Nathalie Koulmann, André-Xavier Bigard
Aug 7, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Clay E PandorfFadia Haddad
Jul 16, 2009·BMC Medical Genomics·Lucas R SmithRichard L Lieber
Nov 19, 2005·Scandinavian Journal of Medicine & Science in Sports·P A Huijing, R T Jaspers
Mar 21, 2006·Journal of Cellular Physiology·Nathalie KoulmannXavier Bigard
Nov 18, 2006·Journal of Cellular Physiology·Joachim D MeissnerRenate J Scheibe
Jan 9, 2009·Journal of Muscle Research and Cell Motility·Boris S Shenkman, T L Nemirovskaya
Jan 27, 2006·American Journal of Physiology. Cell Physiology·Yen-Chih HuangKeith Baar
Feb 20, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Julia GigerFadia Haddad

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