NF-κB but Not FoxO Sites in the MuRF1 Promoter Are Required for Transcriptional Activation in Disuse Muscle Atrophy

Overview

Journal Am J Physiol Cell Physiol

Publisher American Physiological Society

Specialties Cell Biology
Physiology

Date 2014 Feb 21

PMID 24553183

Citations 29

Authors

Chia-Ling Wu

Evangeline W Cornwell

Robert W Jackman

Susan C Kandarian

Affiliations

Soon will be listed here.

Abstract

The muscle-specific ring finger protein 1 (MuRF1) gene is required for most types of skeletal muscle atrophy yet we have little understanding of its transcriptional regulation. The purpose of this study is to identify whether NF-κB and/or FoxO response elements in the MuRF1 promoter are required for MuRF1 gene activation during skeletal muscle atrophy due to the removal of hindlimb weight bearing ("unloading"). Both NF-κB -dependent and FoxO-dependent luciferase reporter activities were significantly increased at 5 days of unloading. Using a 4.4-kb MuRF1 promoter reporter construct, a fourfold increase in reporter (i.e., luciferase) activity was found in rat soleus muscles after 5 days of hindlimb unloading. This activation was abolished by mutagenesis of either of the two distal putative NF-κB sites or all three putative NF-κB sites but not by mutagenesis of all four putative FoxO sites. This work provides the first direct evidence that NF-κB sites, but not FoxO sites, are required for MuRF1 promoter activation in muscle disuse atrophy in vivo.

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References

Plant P, Brooks D, Faughnan M, Bayley T, Bain J, Singer L . Cellular markers of muscle atrophy in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2009; 42(4):461-71. DOI: 10.1165/rcmb.2008-0382OC. View

Hunter R, Kandarian S . Disruption of either the Nfkb1 or the Bcl3 gene inhibits skeletal muscle atrophy. J Clin Invest. 2004; 114(10):1504-11. PMC: 525738. DOI: 10.1172/JCI21696. View

Wu C, Kandarian S, Jackman R . Identification of genes that elicit disuse muscle atrophy via the transcription factors p50 and Bcl-3. PLoS One. 2011; 6(1):e16171. PMC: 3020958. DOI: 10.1371/journal.pone.0016171. View

Baehr L, Furlow J, Bodine S . Muscle sparing in muscle RING finger 1 null mice: response to synthetic glucocorticoids. J Physiol. 2011; 589(Pt 19):4759-76. PMC: 3213422. DOI: 10.1113/jphysiol.2011.212845. View

Schulte L, Navarro J, Kandarian S . Regulation of sarcoplasmic reticulum calcium pump gene expression by hindlimb unweighting. Am J Physiol. 1993; 264(5 Pt 1):C1308-15. DOI: 10.1152/ajpcell.1993.264.5.C1308. View

Bonetto A, Aydogdu T, Kunzevitzky N, Guttridge D, Khuri S, Koniaris L . STAT3 activation in skeletal muscle links muscle wasting and the acute phase response in cancer cachexia. PLoS One. 2011; 6(7):e22538. PMC: 3140523. DOI: 10.1371/journal.pone.0022538. View

Labeit S, Kohl C, Witt C, Labeit D, Jung J, Granzier H . Modulation of muscle atrophy, fatigue and MLC phosphorylation by MuRF1 as indicated by hindlimb suspension studies on MuRF1-KO mice. J Biomed Biotechnol. 2010; 2010:693741. PMC: 2896721. DOI: 10.1155/2010/693741. View

Waddell D, Baehr L, van den Brandt J, Johnsen S, Reichardt H, Furlow J . The glucocorticoid receptor and FOXO1 synergistically activate the skeletal muscle atrophy-associated MuRF1 gene. Am J Physiol Endocrinol Metab. 2008; 295(4):E785-97. PMC: 2652500. DOI: 10.1152/ajpendo.00646.2007. View

Bodine S, Latres E, Baumhueter S, Lai V, Nunez L, Clarke B . Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001; 294(5547):1704-8. DOI: 10.1126/science.1065874. View

10.

Reed S, Senf S, Cornwell E, Kandarian S, Judge A . Inhibition of IkappaB kinase alpha (IKKα) or IKKbeta (IKKβ) plus forkhead box O (Foxo) abolishes skeletal muscle atrophy. Biochem Biophys Res Commun. 2011; 405(3):491-6. PMC: 3056397. DOI: 10.1016/j.bbrc.2011.01.059. View

11.

Files D, DAlessio F, Johnston L, Kesari P, Aggarwal N, Garibaldi B . A critical role for muscle ring finger-1 in acute lung injury-associated skeletal muscle wasting. Am J Respir Crit Care Med. 2012; 185(8):825-34. PMC: 3360571. DOI: 10.1164/rccm.201106-1150OC. View

12.

Reed S, Sandesara P, Senf S, Judge A . Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. FASEB J. 2011; 26(3):987-1000. PMC: 3289501. DOI: 10.1096/fj.11-189977. View

13.

Hoffmann A, Leung T, Baltimore D . Genetic analysis of NF-kappaB/Rel transcription factors defines functional specificities. EMBO J. 2003; 22(20):5530-9. PMC: 213788. DOI: 10.1093/emboj/cdg534. View

14.

Cai D, Frantz J, Tawa Jr N, Melendez P, Oh B, Lidov H . IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell. 2004; 119(2):285-98. DOI: 10.1016/j.cell.2004.09.027. View

15.

Senf S, Dodd S, Judge A . FOXO signaling is required for disuse muscle atrophy and is directly regulated by Hsp70. Am J Physiol Cell Physiol. 2009; 298(1):C38-45. PMC: 2806148. DOI: 10.1152/ajpcell.00315.2009. View

16.

Lecker S, Jagoe R, Gilbert A, Gomes M, Baracos V, Bailey J . Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J. 2004; 18(1):39-51. DOI: 10.1096/fj.03-0610com. View

17.

Brunet A, Bonni A, Zigmond M, Lin M, Juo P, Hu L . Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999; 96(6):857-68. DOI: 10.1016/s0092-8674(00)80595-4. View

18.

Liu C, Yang Z, Liu C, Wang R, Tien P, Dale R . Effect of RNA oligonucleotide targeting Foxo-1 on muscle growth in normal and cancer cachexia mice. Cancer Gene Ther. 2007; 14(12):945-52. DOI: 10.1038/sj.cgt.7701091. View

19.

Stevenson E, Giresi P, Koncarevic A, Kandarian S . Global analysis of gene expression patterns during disuse atrophy in rat skeletal muscle. J Physiol. 2003; 551(Pt 1):33-48. PMC: 2343139. DOI: 10.1113/jphysiol.2003.044701. View

20.

Van Gammeren D, Damrauer J, Jackman R, Kandarian S . The IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy. FASEB J. 2008; 23(2):362-70. PMC: 2630783. DOI: 10.1096/fj.08-114249. View