Multiple muscle wasting-related transcription factors are acetylated in dexamethasone-treated muscle cells

Biochemistry and Cell Biology - Tập 90 Số 2 - Trang 200-208 - 2012
W. L. Chamberlain1, Patricia Gonnella1, Nima Alamdari1, Zaira Aversa1, Per-Olof J. Hasselgren2,1
1Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
2330 Brookline Avenue, ST 919, Boston, MA 02215, USA.

Tóm tắt

Recent studies suggest that the expression and activity of the histone acetyltransferase p300 are upregulated in catabolic muscle allowing for acetylation of cellular proteins. The function of transcription factors is influenced by posttranslational modifications, including acetylation. It is not known if transcription factors involved in the regulation of muscle mass are acetylated in atrophying muscle. We determined cellular levels of acetylated C/EBPβ, C/EBPδ, FOXO1, FOXO3a, and NF-kB/p65 in dexamethasone-treated L6 muscle cells, a commonly used in vitro model of muscle wasting. The role of p300 in dexamethasone-induced transcription factor acetylation and myotube atrophy was examined by transfecting muscle cells with p300 siRNA. Treatment of L6 myotubes with dexamethasone resulted in increased cellular levels of acetylated C/EBPβ and δ, FOXO1 and 3a, and p65. Downregulation of p300 with p300 siRNA reduced acetylation of transcription factors and decreased dexamethasone-induced myotube atrophy and expression of the ubiquitin ligase MuRF1. The results suggest that several muscle wasting-related transcription factors are acetylated supporting the concept that posttranslational modifications of proteins regulating gene transcription may be involved in the loss of muscle mass. The results also suggest that acetylation of the transcription factors is at least in part regulated by p300 and plays a role in glucocorticoid-induced muscle atrophy. Targeting molecules that regulate acetylation of transcription factors may help reduce the impact of muscle wasting.

Từ khóa


Tài liệu tham khảo

10.1152/ajpregu.00858.2009

An M.R., 1996, Mol. Cell. Biol., 16, 2295, 10.1128/MCB.16.5.2295

10.1128/MCB.00180-10

10.1073/pnas.0405454101

10.1126/science.1094637

10.1093/nar/gkn003

10.1016/j.cell.2004.09.027

10.1074/jbc.M511451200

10.1016/j.mce.2008.03.009

10.1007/s00109-003-0469-0

10.1126/science.1175371

10.1073/pnas.0400593101

10.1016/0092-8674(91)90531-3

Fukuoka M., 2003, Int. J. Mol. Med., 12, 503

10.1002/jemt.10213

10.1002/jcb.23093

10.1161/CIRCRESAHA.110.227371

10.1002/jcp.21190

10.1016/j.biocel.2005.01.017

10.1097/MCO.0b013e32833a5107

10.1080/15216540310001642072

10.1074/jbc.M400674200

10.1096/fj.03-0610com

10.1681/ASN.2006010083

10.1002/jcb.21833

10.1016/S0092-8674(04)00126-6

10.1006/bbrc.2001.4497

Penner G., 2002, Am. J. Physiol. Regul. Integr. Comp. Physiol., 282, R439, 10.1152/ajpregu.00512.2001

10.1210/me.2004-0292

10.1152/ajpcell.00531.2009

10.1016/S0092-8674(04)00400-3

10.1152/ajpcell.00255.2010

10.1677/JOE-07-0606

10.1016/j.biocel.2010.01.006

10.1128/MMBR.64.2.435-459.2000

10.1016/j.bbrc.2005.01.002

10.1152/physrev.00016.2008

10.1002/jcb.21544

10.1042/BJ20040167

10.1016/j.tibs.2004.12.002

10.1096/fj.08-114249

Vo N., 2001, J. Biol. Chem., 276, 13505, 10.1074/jbc.R000025200

10.1074/jbc.M705066200

10.1002/jcp.20684

Welm A.L., 1999, Mol. Cell. Biol., 19, 1695, 10.1128/MCB.19.3.1695

10.1093/emboj/cdg218

10.1073/pnas.0607378104

10.1038/sj.emboj.7600570

10.1002/jcp.20278

10.1002/jcb.20371

Yang H., 2007, Am. J. Physiol. Regul. Integr. Comp. Physiol., 292, R337, 10.1152/ajpregu.00230.2006

Thông tin
Thông tin xuất bản

Biochemistry and Cell Biology

Tập 90 Số 2

200-208

Thông tin tác giả