Literature DB >> 26011798

Sodium Channel Inhibitors Reduce DMPK mRNA and Protein.

Luke Witherspoon1,2, Sean O'Reilly1,2, Jeremiah Hadwen1,2, Nafisa Tasnim1,2, Alex MacKenzie1,2, Faraz Farooq2,3.   

Abstract

Myotonic dystrophy type 1 (DM1) is caused by an expanded trinucleotide (CTG)n tract in the 3' untranslated region (UTR) of the dystrophia myotonica protein kinase (DMPK) gene. This results in the aggregation of an expanded mRNA forming toxic intranuclear foci which sequester splicing factors. We believe down-regulation of DMPK mRNA represents a potential, and as yet unexplored, DM1 therapeutic avenue. Consequently, a computational screen for agents which down-regulate DMPK mRNA was undertaken, unexpectedly identifying the sodium channel blockers mexiletine, prilocaine, procainamide, and sparteine as effective suppressors of DMPK mRNA. Analysis of DMPK mRNA in C2C12 myoblasts following treatment with these agents revealed a reduction in the mRNA levels. In vivo analysis of CD1 mice also showed DMPK mRNA and protein down-regulation. The role of DMPK mRNA suppression in the documented efficacy of this class of compounds in DM1 is worthy of further investigation.
© 2015 Wiley Periodicals, Inc.

Entities:  

Keywords:  drug therapy; drugs; molecular biology; molecular genetics; muscle

Mesh：

Substances：

Year:  2015        PMID： 26011798      PMCID： PMC5351028          DOI： 10.1111/cts.12275

Source DB:  PubMed          Journal:  Clin Transl Sci        ISSN： 1752-8054            Impact factor:   4.689


  24 in total

1.  Myotonic dystrophy kinase modulates skeletal muscle but not cardiac voltage-gated sodium channels.

Authors:  M Chahine; A L George
Journal:  FEBS Lett       Date:  1997-08-04       Impact factor: 4.124

2.  Celecoxib increases SMN and survival in a severe spinal muscular atrophy mouse model via p38 pathway activation.

Authors:  Faraz Farooq; Francisco Abadía-Molina; Duncan MacKenzie; Jeremiah Hadwen; Fahad Shamim; Sean O'Reilly; Martin Holcik; Alex MacKenzie
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3.  Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1.

Authors:  E L Logigian; W B Martens; R T Moxley; M P McDermott; N Dilek; A W Wiegner; A T Pearson; C A Barbieri; C L Annis; C A Thornton; R T Moxley
Journal:  Neurology       Date:  2010-05-04       Impact factor: 9.910

4.  Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice.

Authors:  G Jansen; P J Groenen; D Bächner; P H Jap; M Coerwinkel; F Oerlemans; W van den Broek; B Gohlsch; D Pette; J J Plomp; P C Molenaar; M G Nederhoff; C J van Echteld; M Dekker; A Berns; H Hameister; B Wieringa
Journal:  Nat Genet       Date:  1996-07       Impact factor: 38.330

Review 5.  Pathogenic mechanisms of myotonic dystrophy.

Authors:  Johanna E Lee; Thomas A Cooper
Journal:  Biochem Soc Trans       Date:  2009-12       Impact factor: 5.407

6.  Class I and IV antiarrhythmic drugs and cytosolic calcium regulate mRNA encoding the sodium channel alpha subunit in rat cardiac muscle.

Authors:  H J Duff; J Offord; J West; W A Catterall
Journal:  Mol Pharmacol       Date:  1992-10       Impact factor: 4.436

7.  Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy.

Authors:  Thurman M Wheeler; John D Lueck; Maurice S Swanson; Robert T Dirksen; Charles A Thornton
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8.  Modulation of skeletal muscle sodium channels by human myotonin protein kinase.

Authors:  J P Mounsey; P Xu; J E John; L T Horne; J Gilbert; A D Roses; J R Moorman
Journal:  J Clin Invest       Date:  1995-05       Impact factor: 14.808

9.  Characterization of myotonic dystrophy kinase (DMK) protein in human and rodent muscle and central nervous tissue.

Authors:  E J Whiting; J D Waring; K Tamai; M J Somerville; M Hincke; W A Staines; J E Ikeda; R G Korneluk
Journal:  Hum Mol Genet       Date:  1995-06       Impact factor: 6.150

10.  Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member.

Authors:  J D Brook; M E McCurrach; H G Harley; A J Buckler; D Church; H Aburatani; K Hunter; V P Stanton; J P Thirion; T Hudson
Journal:  Cell       Date:  1992-02-21       Impact factor: 41.582
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