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Calcineurin Co-regulates contractile and metabolic components of slow muscle phenotype.
J Biol Chem. 2000 Jun 30; 275(26):19653-60.JB

Abstract

Activation of the transcription factor nuclear factor of activated T cells by the calcium-sensitive serine/threonine phosphatase calcineurin has been proposed as one of the molecular mechanisms by which motor nerve activity establishes the slow muscle phenotype. To investigate whether the calcineurin pathway can regulate the large spectrum of slow muscle characteristics in vivo, we treated rats for three weeks with cyclosporin A (an inhibitor of calcineurin). In soleus (slow muscle), but not in plantaris (fast muscle), the proportion of slow myosin heavy chain (MHC-1) and slow sarcoplasmic reticulum ATPase (SERCA2a) was decreased, whereas that of fast MHC (MHC-2A) and fast SERCA1 increased, indicating a slow to fast contractile phenotype transition. Cytosolic isoforms of creatine kinase and lactate dehydrogenase (most abundant in fast fibers), as well as mitochondrial creatine kinase and citrate synthase activities (elevated in fast/oxidative fibers) were dose dependently increased by cyclosporin A treatment in soleus muscle, with no change in plantaris. Calcineurin catalytic subunit was more abundant in soleus muscle fibers compared with plantaris. Taken together these results suggest that the calcineurin pathway co-regulates a set of multigenic protein families involved in the transition between slow oxidative (type I) to fast oxidative (type IIa) phenotype in soleus muscle.

Authors+Show Affiliations

Unité de Bioénergétique et Environnement, Centre de Recherches du Service de Santé des Armées, Avenue du Maquis du Grésivaudan, 38702, La Tronche Cedex, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10777482

Citation

Bigard, X, et al. "Calcineurin Co-regulates Contractile and Metabolic Components of Slow Muscle Phenotype." The Journal of Biological Chemistry, vol. 275, no. 26, 2000, pp. 19653-60.
Bigard X, Sanchez H, Zoll J, et al. Calcineurin Co-regulates contractile and metabolic components of slow muscle phenotype. J Biol Chem. 2000;275(26):19653-60.
Bigard, X., Sanchez, H., Zoll, J., Mateo, P., Rousseau, V., Veksler, V., & Ventura-Clapier, R. (2000). Calcineurin Co-regulates contractile and metabolic components of slow muscle phenotype. The Journal of Biological Chemistry, 275(26), 19653-60.
Bigard X, et al. Calcineurin Co-regulates Contractile and Metabolic Components of Slow Muscle Phenotype. J Biol Chem. 2000 Jun 30;275(26):19653-60. PubMed PMID: 10777482.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcineurin Co-regulates contractile and metabolic components of slow muscle phenotype. AU - Bigard,X, AU - Sanchez,H, AU - Zoll,J, AU - Mateo,P, AU - Rousseau,V, AU - Veksler,V, AU - Ventura-Clapier,R, PY - 2000/4/25/pubmed PY - 2000/8/12/medline PY - 2000/4/25/entrez SP - 19653 EP - 60 JF - The Journal of biological chemistry JO - J Biol Chem VL - 275 IS - 26 N2 - Activation of the transcription factor nuclear factor of activated T cells by the calcium-sensitive serine/threonine phosphatase calcineurin has been proposed as one of the molecular mechanisms by which motor nerve activity establishes the slow muscle phenotype. To investigate whether the calcineurin pathway can regulate the large spectrum of slow muscle characteristics in vivo, we treated rats for three weeks with cyclosporin A (an inhibitor of calcineurin). In soleus (slow muscle), but not in plantaris (fast muscle), the proportion of slow myosin heavy chain (MHC-1) and slow sarcoplasmic reticulum ATPase (SERCA2a) was decreased, whereas that of fast MHC (MHC-2A) and fast SERCA1 increased, indicating a slow to fast contractile phenotype transition. Cytosolic isoforms of creatine kinase and lactate dehydrogenase (most abundant in fast fibers), as well as mitochondrial creatine kinase and citrate synthase activities (elevated in fast/oxidative fibers) were dose dependently increased by cyclosporin A treatment in soleus muscle, with no change in plantaris. Calcineurin catalytic subunit was more abundant in soleus muscle fibers compared with plantaris. Taken together these results suggest that the calcineurin pathway co-regulates a set of multigenic protein families involved in the transition between slow oxidative (type I) to fast oxidative (type IIa) phenotype in soleus muscle. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/10777482/Calcineurin_Co_regulates_contractile_and_metabolic_components_of_slow_muscle_phenotype_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(19)80032-7 DB - PRIME DP - Unbound Medicine ER -