Patterns of gene expression in atrophying skeletal muscles: response to food deprivation

被引:260
作者
Jagoe, RT
Lecker, SH
Gomes, M
Goldberg, AL
机构
[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[2] Beth Israel Deaconess Med Ctr, Renal Unit, Boston, MA 02215 USA
关键词
cDNA microarray; ubiquitin; proteasome; cachexia;
D O I
10.1096/fj.02-0312com
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
During fasting and many systemic diseases, muscle undergoes rapid loss of protein and functional capacity. To define the transcriptional changes triggering muscle atrophy and energy conservation in fasting, we used cDNA microarrays to compare mRNAs from muscles of control and food-deprived mice. Expression of >94% of genes did not change, but interesting patterns emerged among genes that were differentially expressed: 1) mRNAs encoding polyubiquitin, ubiquitin extension proteins, and many (but not all) proteasome subunits increased, which presumably contributes to accelerated protein breakdown; 2) a dramatic increase in mRNA for the ubiquitin ligase, atrogin-1, but not most E3s; 3) a significant suppression of mRNA for myosin binding protein H (but not other myofibrillar proteins) and IGF binding protein 5, which may favor cell protein loss; 4) decreases in mRNAs for several glycolytic enzymes and phosphorylase kinase subunits, and dramatic increases in mRNAs for pyruvate dehydrogenase kinase 4 and glutamine synthase, which should promote glucose sparing and gluconeogenesis. During fasting, metallothionein mRNA increased dramatically, mRNAs for extracellular matrix components fell, and mRNAs that may favor cap-independent mRNA translation rose. Significant changes occurred in mRNAs for many growth-related proteins and transcriptional regulators. These transcriptional changes indicate a complex adaptive program that should favor protein degradation and suppress glucose oxidation in muscle. Similar analysis of muscles atrophying for other causes is allowing us to identify a set of atrophy-specific changes in gene expression.
引用
收藏
页码:1697 / 1712
页数:16
相关论文
共 98 条
  • [91] Sepsis stimulates release of myofilaments in skeletal muscle by a calcium-dependent mechanism
    Williams, AB
    Decourten-Myers, GM
    Fischer, JE
    Luo, GJ
    Sun, XY
    Hasselgren, PO
    [J]. FASEB JOURNAL, 1999, 13 (11) : 1435 - 1443
  • [92] 14-KDA UBIQUITIN-CONJUGATING ENZYME - STRUCTURE OF THE RAT GENE AND REGULATION UPON FASTING AND BY INSULIN
    WING, SS
    BANVILLE, D
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 267 (01): : E39 - E48
  • [93] GLUCOCORTICOIDS ACTIVATE THE ATP-UBIQUITIN-DEPENDENT PROTEOLYTIC SYSTEM IN SKELETAL-MUSCLE DURING FASTING
    WING, SS
    GOLDBERG, AL
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 264 (04): : E668 - E676
  • [94] Prolonged unloading of rat soleus muscle causes distinct adaptations of the gene profile
    Wittwer, M
    Flück, M
    Hoppeler, H
    Müller, S
    Desplanches, D
    Billeter, R
    [J]. FASEB JOURNAL, 2002, 16 (06) : 884 - +
  • [95] Starvation increases the amount of pyruvate dehydrogenase kinase in several mammalian tissues
    Wu, PF
    Blair, PV
    Sato, J
    Jaskiewicz, J
    Popov, KM
    Harris, RA
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2000, 381 (01) : 1 - 7
  • [96] Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes
    Wu, PF
    Inskeep, K
    Bowker-Kinley, MM
    Popov, KM
    Harris, RA
    [J]. DIABETES, 1999, 48 (08) : 1593 - 1599
  • [97] Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart
    Wu, PF
    Sato, J
    Zhao, Y
    Jaskiewicz, J
    Popov, KM
    Harris, RA
    [J]. BIOCHEMICAL JOURNAL, 1998, 329 : 197 - 201
  • [98] YOKOTA S, 1990, HISTOCHEMISTRY, V93, P287