title: Changes in REDD1, REDD2, and atrogene mRNA expression are prevented in skeletal muscle fixed in a stretched position during hindlimb immobilization.
abstract: Immobilized skeletal muscle fixed in a shortened position displays disuse atrophy, whereas when fixed in a stretched position it does not (Goldspink, D. F. (1977) J Physiol 264, 267-282). Although significant advances have been made in our understanding of mechanisms involved in development of atrophy in muscle fixed in a shortened position, little is known about why mass is maintained when muscle is immobilized in a stretched position. In the present study, we hypothesized that skeletal muscle immobilized in a stretched position would be protected from gene expression changes known to be associated with disuse atrophy. To test the hypothesis, male Sprague-Dawley rats were anesthetized using isoflurane and subjected to unilateral hindlimb immobilization for 3 days with the soleus fixed in either a shortened or stretched position. All comparisons were made to the contralateral nonimmobilized muscle. Soleus immobilized in a shortened position exhibited disuse atrophy, attenuated rates of protein synthesis, attenuated mTORC1 signaling, and induced expression of genes for REDD1, REDD2, MAFbx, and MuRF1. In contrast, immobilization of the soleus in a stretched position prevented these changes as it exhibited no difference in muscle mass, rates of protein synthesis, mTORC1 signaling, or expression of genes encoding REDD1, MAFbx or MuRF1, with REDD2 expression being reduced compared to control. In conclusion, fixed muscle length plays a major role in immobilization-induced skeletal muscle atrophy whereby placing muscle in a shortened position leads to induction of gene expression for REDD1, REDD2, and atrogenes.
authors.affiliation: Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Kelleher
authors.affiliation: Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Gordon
authors.affiliation: Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Scot R
authors.initials: SR
authors.lastname: Kimball
authors.affiliation: Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Jefferson
keywords: Casting; Ddit4; Ddit4l; disuse atrophy; mTORC1
references.citation: Biochem J. 2004 Jun 15;380(Pt 3):795-804
references.pmid: 15030312
references.citation: J Appl Physiol (1985). 1986 Jul;61(1):173-9
references.pmid: 3733601
references.citation: Int J Biochem Cell Biol. 2013 Oct;45(10):2200-8
references.pmid: 23800384
references.citation: Appl Physiol Nutr Metab. 2010 Jun;35(3):310-8
references.pmid: 20555375
references.citation: Am J Physiol Cell Physiol. 2009 Mar;296(3):C583-92
references.pmid: 19129461
references.citation: Am J Phys Med Rehabil. 2004 Nov;83(11):851-6
references.pmid: 15502738
references.citation: FASEB J. 2008 Nov;22(11):3836-45
references.pmid: 18644837
references.citation: Eur J Appl Physiol. 2011 Aug;111(8):1815-28
references.pmid: 21222129
references.citation: Am J Physiol. 1992 Mar;262(3 Pt 2):R356-63
references.pmid: 1373039
references.citation: Am J Physiol Endocrinol Metab. 2013 Jan 15;304(2):E229-36
references.pmid: 23193052
references.citation: Int J Biochem Cell Biol. 2013 Oct;45(10):2147-57
references.pmid: 23769967
references.citation: Muscle Nerve. 2009 Apr;39(4):456-62
references.pmid: 19260063
references.citation: Biochem J. 1978 Aug 15;174(2):595-602
references.pmid: 708412
references.citation: Am J Physiol Endocrinol Metab. 2012 May 15;302(9):E1113-22
references.pmid: 22338078
references.citation: Appl Physiol Nutr Metab. 2009 Jun;34(3):377-81
references.pmid: 19448702
references.citation: Am J Physiol Cell Physiol. 2010 Jan;298(1):C38-45
references.pmid: 19864323
references.citation: Pflugers Arch. 1998 May;435(6):850-8
references.pmid: 9518515
references.citation: Muscle Nerve. 2010 Jan;41(1):100-6
references.pmid: 19768770
references.citation: J Appl Physiol (1985). 2009 Sep;107(3):645-54
references.pmid: 19608931
references.citation: J Biol Chem. 2010 Sep 17;285(38):29027-32
references.pmid: 20576612
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1977 Oct;43(4):656-61
references.pmid: 198396
references.citation: Pflugers Arch. 2011 Jul;462(1):119-34
references.pmid: 21416260
references.citation: J Cell Physiol. 2006 Sep;208(3):575-85
references.pmid: 16741926
references.citation: Physiology (Bethesda). 2010 Jun;25(3):186-98
references.pmid: 20551232
references.citation: J Physiol. 1977 Jan;264(1):267-82
references.pmid: 839454
references.citation: Int J Biochem Cell Biol. 2013 Oct;45(10):2121-9
references.pmid: 23665154
references.citation: Muscle Nerve. 2007 Nov;36(5):685-93
references.pmid: 17657803
references.citation: Am J Physiol. 1998 Dec;275(6):C1438-48
references.pmid: 9843704
references.citation: FASEB J. 2011 Mar;25(3):1028-39
references.pmid: 21148113
references.citation: Muscle Nerve. 2010 Jun;41(6):800-8
references.pmid: 20082419
references.citation: J Nutr. 2005 Jul;135(7):1824S-1828S
references.pmid: 15987873
references.citation: Science. 2001 Nov 23;294(5547):1704-8
references.pmid: 11679633
references.citation: Mol Cell Biol. 2005 Jul;25(14):5834-45
references.pmid: 15988001
references.citation: Genes Dev. 2003 Aug 1;17(15):1829-34
references.pmid: 12869586
references.citation: J Physiol. 1978 Jul;280:64P-65P
references.pmid: 690927
references.citation: J Physiol. 2008 Dec 15;586(24):6049-61
references.pmid: 18955382