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Calcineurin enhances acetylcholinesterase mRNA stability during C2-C12 muscle cell differentiation.

Publication ,  Journal Article
Luo, ZD; Wang, Y; Werlen, G; Camp, S; Chien, KR; Taylor, P
Published in: Mol Pharmacol
November 1999

Treatment of C2-C12 mouse myoblasts with the immunosuppressant drug cyclosporin A (CsA) enhances the increase in acetylcholinesterase (AChE) expression observed during skeletal muscle differentiation. The enhanced AChE expression is due primarily to increased mRNA stability because CsA treatment increases the half-life of AChE mRNA, but not the apparent transcriptional rate of the gene. Neither tacrolimus (FK506), an immunosuppressive agent with a distinct structure, nor cyclosporine H, an inactive congener of CsA, alters AChE expression. The enhanced AChE expression is associated with the muscle differentiation process, but cannot be triggered by CsA exposure before differentiation. Myoblasts and myotubes of C2-C12 cells express similar amounts of cyclophilin A and FKBP12, immunophilins known to be intracellular-binding targets for CsA and tacrolimus, respectively. However, cellular levels of calcineurin, a calcium/calmodulin-dependent phosphatase known to be the cellular target of ligand-immunophilin complexes, increase 3-fold during myogenesis. Overexpression of constitutively active calcineurin in differentiating cells reduces AChE mRNA levels and CsA antagonizes such an inhibition. Conversely, overexpression of a dominant negative calcineurin construct increases AChE mRNA levels, which are further enhanced by CsA. Thus, a CsA sensitive, calcineurin mediated pathway appears linked to differentiation-induced stabilization of AChE mRNA during myogenesis.

Duke Scholars

Published In

Mol Pharmacol

ISSN

0026-895X

Publication Date

November 1999

Volume

56

Issue

5

Start / End Page

886 / 894

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • RNA, Messenger
  • RNA Stability
  • Pharmacology & Pharmacy
  • Muscles
  • Mice
  • Immunophilins
  • Cyclosporine
  • Cells, Cultured
  • Cell Differentiation
 

Citation

APA
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ICMJE
MLA
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Luo, Z. D., Wang, Y., Werlen, G., Camp, S., Chien, K. R., & Taylor, P. (1999). Calcineurin enhances acetylcholinesterase mRNA stability during C2-C12 muscle cell differentiation. Mol Pharmacol, 56(5), 886–894.
Luo, Z. D., Y. Wang, G. Werlen, S. Camp, K. R. Chien, and P. Taylor. “Calcineurin enhances acetylcholinesterase mRNA stability during C2-C12 muscle cell differentiation.Mol Pharmacol 56, no. 5 (November 1999): 886–94.
Luo ZD, Wang Y, Werlen G, Camp S, Chien KR, Taylor P. Calcineurin enhances acetylcholinesterase mRNA stability during C2-C12 muscle cell differentiation. Mol Pharmacol. 1999 Nov;56(5):886–94.
Luo, Z. D., et al. “Calcineurin enhances acetylcholinesterase mRNA stability during C2-C12 muscle cell differentiation.Mol Pharmacol, vol. 56, no. 5, Nov. 1999, pp. 886–94.
Luo ZD, Wang Y, Werlen G, Camp S, Chien KR, Taylor P. Calcineurin enhances acetylcholinesterase mRNA stability during C2-C12 muscle cell differentiation. Mol Pharmacol. 1999 Nov;56(5):886–894.

Published In

Mol Pharmacol

ISSN

0026-895X

Publication Date

November 1999

Volume

56

Issue

5

Start / End Page

886 / 894

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • RNA, Messenger
  • RNA Stability
  • Pharmacology & Pharmacy
  • Muscles
  • Mice
  • Immunophilins
  • Cyclosporine
  • Cells, Cultured
  • Cell Differentiation