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Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle.
Am J Physiol Regul Integr Comp Physiol. 2009 Oct; 297(4):R1037-48.AJ

Abstract

The role of calcineurin (Cn) in skeletal muscle fiber-type expression has been a subject of great interest because of reports indicating that it controls the slow muscle phenotype. To delineate the role of Cn in phenotype remodeling, particularly its role in driving expression of the type I myosin heavy chain (MHC) gene, we used a novel strategy whereby a profound transition from fast to slow fiber type is induced and examined in the absence and presence of cyclosporin A (CsA), a Cn inhibitor. To induce the fast-to-slow transition, we first subjected rats to 7 days of hindlimb suspension (HS) + thyroid hormone [triiodothyronine (T(3))] to suppress nearly all expression of type I MHC mRNA in the soleus muscle. HS + T(3) was then withdrawn, and rats resumed normal ambulation and thyroid state, during which vehicle or CsA (30 mg x kg(-1) x day(-1)) was administered for 7 or 14 days. The findings demonstrate that, despite significant inhibition of Cn, pre-mRNA, mRNA, and protein abundance of type I MHC increased markedly during reloading relative to HS + T(3) (P < 0.05). Type I MHC expression was, however, attenuated by CsA compared with vehicle treatment. In addition, type IIa and IIx MHC pre-mRNA, mRNA, and relative protein levels were increased in Cn-treated compared with vehicle-treated rats. These findings indicate that Cn has a modulatory role in MHC transcription, rather than a role as a primary regulator of slow MHC gene expression.

Authors+Show Affiliations

Department of Physiology and Biophysics, University of California, Irvine, Irvine, California 92697, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19657098

Citation

Pandorf, Clay E., et al. "Calcineurin Plays a Modulatory Role in Loading-induced Regulation of Type I Myosin Heavy Chain Gene Expression in Slow Skeletal Muscle." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 297, no. 4, 2009, pp. R1037-48.
Pandorf CE, Jiang WH, Qin AX, et al. Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2009;297(4):R1037-48.
Pandorf, C. E., Jiang, W. H., Qin, A. X., Bodell, P. W., Baldwin, K. M., & Haddad, F. (2009). Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 297(4), R1037-48. https://doi.org/10.1152/ajpregu.00349.2009
Pandorf CE, et al. Calcineurin Plays a Modulatory Role in Loading-induced Regulation of Type I Myosin Heavy Chain Gene Expression in Slow Skeletal Muscle. Am J Physiol Regul Integr Comp Physiol. 2009;297(4):R1037-48. PubMed PMID: 19657098.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle. AU - Pandorf,Clay E, AU - Jiang,Weihua H, AU - Qin,Anqi X, AU - Bodell,Paul W, AU - Baldwin,Kenneth M, AU - Haddad,Fadia, Y1 - 2009/08/05/ PY - 2009/8/7/entrez PY - 2009/8/7/pubmed PY - 2009/10/14/medline SP - R1037 EP - 48 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am J Physiol Regul Integr Comp Physiol VL - 297 IS - 4 N2 - The role of calcineurin (Cn) in skeletal muscle fiber-type expression has been a subject of great interest because of reports indicating that it controls the slow muscle phenotype. To delineate the role of Cn in phenotype remodeling, particularly its role in driving expression of the type I myosin heavy chain (MHC) gene, we used a novel strategy whereby a profound transition from fast to slow fiber type is induced and examined in the absence and presence of cyclosporin A (CsA), a Cn inhibitor. To induce the fast-to-slow transition, we first subjected rats to 7 days of hindlimb suspension (HS) + thyroid hormone [triiodothyronine (T(3))] to suppress nearly all expression of type I MHC mRNA in the soleus muscle. HS + T(3) was then withdrawn, and rats resumed normal ambulation and thyroid state, during which vehicle or CsA (30 mg x kg(-1) x day(-1)) was administered for 7 or 14 days. The findings demonstrate that, despite significant inhibition of Cn, pre-mRNA, mRNA, and protein abundance of type I MHC increased markedly during reloading relative to HS + T(3) (P < 0.05). Type I MHC expression was, however, attenuated by CsA compared with vehicle treatment. In addition, type IIa and IIx MHC pre-mRNA, mRNA, and relative protein levels were increased in Cn-treated compared with vehicle-treated rats. These findings indicate that Cn has a modulatory role in MHC transcription, rather than a role as a primary regulator of slow MHC gene expression. SN - 1522-1490 UR - https://www.unboundmedicine.com/medline/citation/19657098/Calcineurin_plays_a_modulatory_role_in_loading_induced_regulation_of_type_I_myosin_heavy_chain_gene_expression_in_slow_skeletal_muscle_ L2 - https://journals.physiology.org/doi/10.1152/ajpregu.00349.2009?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -