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Calcineurin activation influences muscle phenotype in a muscle-specific fashion.
BMC Cell Biol. 2004 Jul 28; 5:28.BC

Abstract

BACKGROUND

The calcium activated protein phosphatase 2B, also known as calcineurin, has been implicated as a cell signaling molecule involved with transduction of physiological signals (free cytosolic Ca2+) into molecular signals that influence the expression of phenotype-specific genes in skeletal muscle. In the present study we address the role of calcineurin in mediating adaptations in myosin heavy chain (MHC) isoform expression and muscle mass using 3-month old wild-type (WT) and transgenic mice displaying high-level expression of a constitutively active form of calcineurin (MCK-CN* mice).

RESULTS

Slow muscles, e.g., soleus, were significantly larger (by ~24%), whereas fast muscles, e.g., medial gastrocnemius (MG) and tibialis anterior were significantly smaller (by ~26 and ~16%, respectively) in MCK-CN* mice compared to WT. The masses of mixed phenotype muscles, such as the plantaris and the extensor digitorum longus, were not significantly changed from WT. The soleus, plantaris, MG and diaphragm displayed shifts toward slower MHC isoforms, e.g., soleus from WT mice contained ~52% MHC-I, ~39% MHC-IIa, and ~9% MHC-IIx, whereas MCK-CN* mice had ~67% MHC-I, ~26% MHC-IIa, and ~7% MHC-IIx. The specific isoforms that were either up or down-regulated were muscle-specific. For instance, the proportion of MHC-IIa was decreased in the soleus and diaphragm, but increased in the plantaris and MG of MCK-CN* mice. Also, the proportion of MHC-IIx was unchanged in the soleus, decreased in the diaphragm and increased in the plantaris and MG of MCK-CN* relative to WT mice. Fast to slow shifts in fiber type proportions were evident for the plantaris, but not the soleus. Fast, but not slow, plantaris fibers of MCK-CN* mice had higher oxidative and lower glycolytic properties than WT.

CONCLUSION

These data suggest that calcineurin activation can influence muscle phenotype and that the specific influence of calcineurin activation on the phenotypic and mass characteristics of a muscle is dependent upon the original phenotypic state of the muscle.

Authors+Show Affiliations

Department of Biological Sciences, California State Polytechnic University, Pomona, CA 91768, USA. rjtalmadge@csupomona.eduNo 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, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15282035

Citation

Talmadge, Robert J., et al. "Calcineurin Activation Influences Muscle Phenotype in a Muscle-specific Fashion." BMC Cell Biology, vol. 5, 2004, p. 28.
Talmadge RJ, Otis JS, Rittler MR, et al. Calcineurin activation influences muscle phenotype in a muscle-specific fashion. BMC Cell Biol. 2004;5:28.
Talmadge, R. J., Otis, J. S., Rittler, M. R., Garcia, N. D., Spencer, S. R., Lees, S. J., & Naya, F. J. (2004). Calcineurin activation influences muscle phenotype in a muscle-specific fashion. BMC Cell Biology, 5, 28.
Talmadge RJ, et al. Calcineurin Activation Influences Muscle Phenotype in a Muscle-specific Fashion. BMC Cell Biol. 2004 Jul 28;5:28. PubMed PMID: 15282035.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcineurin activation influences muscle phenotype in a muscle-specific fashion. AU - Talmadge,Robert J, AU - Otis,Jeffrey S, AU - Rittler,Matthew R, AU - Garcia,Nicole D, AU - Spencer,Shelly R, AU - Lees,Simon J, AU - Naya,Francisco J, Y1 - 2004/07/28/ PY - 2004/05/10/received PY - 2004/07/28/accepted PY - 2004/7/30/pubmed PY - 2005/1/27/medline PY - 2004/7/30/entrez SP - 28 EP - 28 JF - BMC cell biology JO - BMC Cell Biol VL - 5 N2 - BACKGROUND: The calcium activated protein phosphatase 2B, also known as calcineurin, has been implicated as a cell signaling molecule involved with transduction of physiological signals (free cytosolic Ca2+) into molecular signals that influence the expression of phenotype-specific genes in skeletal muscle. In the present study we address the role of calcineurin in mediating adaptations in myosin heavy chain (MHC) isoform expression and muscle mass using 3-month old wild-type (WT) and transgenic mice displaying high-level expression of a constitutively active form of calcineurin (MCK-CN* mice). RESULTS: Slow muscles, e.g., soleus, were significantly larger (by ~24%), whereas fast muscles, e.g., medial gastrocnemius (MG) and tibialis anterior were significantly smaller (by ~26 and ~16%, respectively) in MCK-CN* mice compared to WT. The masses of mixed phenotype muscles, such as the plantaris and the extensor digitorum longus, were not significantly changed from WT. The soleus, plantaris, MG and diaphragm displayed shifts toward slower MHC isoforms, e.g., soleus from WT mice contained ~52% MHC-I, ~39% MHC-IIa, and ~9% MHC-IIx, whereas MCK-CN* mice had ~67% MHC-I, ~26% MHC-IIa, and ~7% MHC-IIx. The specific isoforms that were either up or down-regulated were muscle-specific. For instance, the proportion of MHC-IIa was decreased in the soleus and diaphragm, but increased in the plantaris and MG of MCK-CN* mice. Also, the proportion of MHC-IIx was unchanged in the soleus, decreased in the diaphragm and increased in the plantaris and MG of MCK-CN* relative to WT mice. Fast to slow shifts in fiber type proportions were evident for the plantaris, but not the soleus. Fast, but not slow, plantaris fibers of MCK-CN* mice had higher oxidative and lower glycolytic properties than WT. CONCLUSION: These data suggest that calcineurin activation can influence muscle phenotype and that the specific influence of calcineurin activation on the phenotypic and mass characteristics of a muscle is dependent upon the original phenotypic state of the muscle. SN - 1471-2121 UR - https://www.unboundmedicine.com/medline/citation/15282035/Calcineurin_activation_influences_muscle_phenotype_in_a_muscle_specific_fashion_ L2 - https://bmccellbiol.biomedcentral.com/articles/10.1186/1471-2121-5-28 DB - PRIME DP - Unbound Medicine ER -