| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology and Biophysics, University of California-Irvine, Irvine, CA, USA
2 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, USA
* To whom correspondence should be addressed. E-mail: kmbaldwi{at}uci.edu.
Skeletal muscle-derived insulin-like growth factor I (IGF-I) expression plays a significant role in mediating muscle hypertrophy induced by mechanical loading. The present study investigated the role of transcription in the regulation of IGF-I expression in skeletal muscle. RT-PCR was used to determine endogenous expression of IGF-I pre-mRNA and mRNA in control (Con) and functionally overloaded (FO) rat plantaris (P). The transcriptional activities of five different length IGF-I promoter fragments controlling transcription of a firefly luciferase (FLuc) reporter gene were tested in vitro by transfection of either C2C12 and L6E9 myoblasts or in vivo during FO using direct gene transfer into the P. Increased endogenous IGF-I gene transcription during 7 d of P FO was evidenced by an ~140-160% increase (P<0.0001) in IGF-I pre-mRNA (a transcriptional marker). IGF-I mRNA expression also increased by ~90% (P<0.0001), and it was correlated (R=0.93; P<0.0001) with the pre-mRNA increases. The three longest IGF-I exon 1 promoters induced reporter gene expression in proliferating C2C12 and L6E9 myoblasts. In differentiated L6E9 myotubes, promoter activity increased ~2-3 fold over myoblasts. Over-expression of calcinuerin and myoD increased the activity of the -852/+192 promoter in C2C12 myotubes by ~5- and ~18-fold, respectively. However, FO did not induce these exogenous promoter fragments, and only the two longest promoter constructs exhibited a low level of activity in Con muscle. Nevertheless, the present findings are consistent with the hypothesis that the IGF-I gene is transcriptionally regulated during muscle hypertrophy in vivo as evidenced by the induction of the endogenous IGF-I pre-mRNA during P FO. The exon 1 promoter region of the IGF-I gene is sufficient to direct inducible expression in vitro, however, an in vivo response to FO requires elements outside the -852/+346 region of the exon 1 IGF-I promoter. Alternatively, there may be additional features inherent to the endogenous IGF-I gene, but absent from these promoter-reporter plasmid constructs, that are required to induce transcription in vivo.
This article has been cited by other articles:
|
|
 |
|
  H. Choi, P.-J. I. Selpides, M. M. Nowell, and B. C. Rourke Functional overload in ground squirrel plantaris muscle fails to induce myosin isoform shifts Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R578 - R586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Matheny, E. Merritt, S. V. Zannikos, R. P. Farrar, and M. L. Adamo Serum IGF-I-Deficiency Does Not Prevent Compensatory Skeletal Muscle Hypertrophy in Resistance Exercise Experimental Biology and Medicine, February 1, 2009; 234(2): 164 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sandri Signaling in Muscle Atrophy and Hypertrophy Physiology, June 1, 2008; 23(3): 160 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Deldicque, D. Theisen, L. Bertrand, P. Hespel, L. Hue, and M. Francaux Creatine enhances differentiation of myogenic C2C12 cells by activating both p38 and Akt/PKB pathways Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1263 - C1271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Fernandez, S. Fernandez, P. Carrero, M. Garcia-Garcia, and I. Torres-Aleman Calcineurin in Reactive Astrocytes Plays a Key Role in the Interplay between Proinflammatory and Anti-Inflammatory Signals J. Neurosci., August 15, 2007; 27(33): 8745 - 8756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Alfieri, H. J. Evans-Anderson, and K. E. Yutzey Developmental regulation of the mouse IGF-I exon 1 promoter region by calcineurin activation of NFAT in skeletal muscle Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1887 - C1894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. McLellan, T. Kealey, and K. Langlands An E box in the exon 1 promoter regulates insulin-like growth factor-I expression in differentiating muscle cells Am J Physiol Cell Physiol, August 1, 2006; 291(2): C300 - C307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Goldspink Mechanical Signals, IGF-I Gene Splicing, and Muscle Adaptation Physiology, August 1, 2005; 20(4): 232 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. J. Caiozzo, Y. Z. Wu, M. J. Baker, and R. Crumley Effects of Denervation on Cell Cycle Control in Laryngeal Muscle Arch Otolaryngol Head Neck Surg, September 1, 2004; 130(9): 1056 - 1068. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
