| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of Cellular and Molecular Physiology, and Surgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
The present study examined potential mechanisms
contributing to the inhibition of protein synthesis in skeletal muscle
after administration of endotoxin (LPS). Rats implanted with vascular catheters were injected intravenously with a nonlethal dose of Escherichia coli LPS, and samples were collected at 4 and 24 h thereafter; pair-fed control animals were also included. The rate of
muscle (gastrocnemius) protein synthesis in vivo was reduced at both
time points after LPS administration. LPS did not alter tissue RNA
content, but the translational efficiency was consistently reduced at
both time points. To identify mechanisms responsible for regulating
translation, we examined several eukaryotic initiation factors (eIFs).
The content of eIF2
or the amount of eIF2 in the phosphorylated
form did not change in response to LPS. eIF2B activity was decreased in
muscle 4 h post-LPS but activity returned to control values by 24 h. A
decrease in the relative amount of eIF2B protein was not responsible
for the LPS-induced reduction in eIF2B activity. LPS also markedly
altered the distribution of eIF4E in muscle. Compared with control
values, LPS-treated rats demonstrated 1) a transient increase
in binding of the translation repressor 4E-binding protein-1 (4E-BP1)
with eIF4E, 2) a transient decrease in the phosphorylated
-form of 4E-BP1, and 3) a sustained decrease in the amount
of eIF4G associated with eIF4E. LPS also decreased insulin-like growth
factor (IGF) I protein and mRNA expression in muscle at both times. A
significant linear relationship existed between muscle IGF-I and the
rate of protein synthesis or the amount of eIF4E bound to eIF4G. In
summary, these data suggest that LPS impairs muscle protein synthesis,
at least in part, by decreasing translational efficiency, resulting
from an impairment in translation initiation associated with
alterations in both eIF2B activity and eIF4E availability.
eukaryotic initiation factors; eukaryotic initiation factor 2; eukaryotic initiation factor 4E; peptide-chain initiation; lipopolysaccharide; heart; liver; insulin-like growth factor I; rats
This article has been cited by other articles:
|
|
 |
|
  H. L. Eley, S. T. Russell, and M. J. Tisdale Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by {beta}-hydroxy-{beta}-methylbutyrate Am J Physiol Endocrinol Metab, December 1, 2008; 295(6): E1409 - E1416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Pruznak, A. A. Kazi, R. A. Frost, T. C. Vary, and C. H. Lang Activation of AMP-Activated Protein Kinase by 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribonucleoside Prevents Leucine-Stimulated Protein Synthesis in Rat Skeletal Muscle J. Nutr., October 1, 2008; 138(10): 1887 - 1894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Frost and C. H. Lang Regulation of muscle growth by pathogen-associated molecules J Anim Sci, April 1, 2008; 86(14_suppl): E84 - E93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Orellana, A. Jeyapalan, J. Escobar, J. W. Frank, H. V. Nguyen, A. Suryawan, and T. A. Davis Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1416 - E1425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Vary Acute Oral Leucine Administration Stimulates Protein Synthesis during Chronic Sepsis through Enhanced Association of Eukaryotic Initiation Factor 4G with Eukaryotic Initiation Factor 4E in Rats J. Nutr., September 1, 2007; 137(9): 2074 - 2079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Lang, R. A. Frost, and T. C. Vary Regulation of muscle protein synthesis during sepsis and inflammation Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E453 - E459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Frost, G. J. Nystrom, L. S. Jefferson, and C. H. Lang Hormone, cytokine, and nutritional regulation of sepsis-induced increases in atrogin-1 and MuRF1 in skeletal muscle Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E501 - E512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Orellana, S. R. Kimball, A. Suryawan, J. Escobar, H. V. Nguyen, L. S. Jefferson, and T. A. Davis Insulin stimulates muscle protein synthesis in neonates during endotoxemia despite repression of translation initiation Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E629 - E636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Lang, D. Huber, and R. A. Frost Burn-induced increase in atrogin-1 and MuRF-1 in skeletal muscle is glucocorticoid independent but downregulated by IGF-I Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R328 - R336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Orellana, P. M. J. O'Connor, J. A. Bush, A. Suryawan, M. C. Thivierge, H. V. Nguyen, M. L. Fiorotto, and T. A. Davis Modulation of muscle protein synthesis by insulin is maintained during neonatal endotoxemia Am J Physiol Endocrinol Metab, July 1, 2006; 291(1): E159 - E166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Vary IGF-I stimulates protein synthesis in skeletal muscle through multiple signaling pathways during sepsis Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2006; 290(2): R313 - R321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Q. Hong-Brown, A. M. Pruznak, R. A. Frost, T. C. Vary, and C. H. Lang Indinavir alters regulators of protein anabolism and catabolism in skeletal muscle Am J Physiol Endocrinol Metab, September 1, 2005; 289(3): E382 - E390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Williamson, S. R. Kimball, and L. S. Jefferson Acute treatment with TNF-{alpha} attenuates insulin-stimulated protein synthesis in cultures of C2C12 myotubes through a MEK1-sensitive mechanism Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E95 - E104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. C. Luiking, M. M. Hallemeesch, W. H. Lamers, and N. E. P. Deutz NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1258 - E1264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Lang and R. A. Frost Differential effect of sepsis on ability of leucine and IGF-I to stimulate muscle translation initiation Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E721 - E730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Lang, R. A. Frost, and T. C. Vary Thermal injury impairs cardiac protein synthesis and is associated with alterations in translation initiation Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2004; 286(4): R740 - R750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Priego, I. Ibanez de Caceres, A. I. Martin, M. A. Villanua, and A. Lopez-Calderon NO plays a role in LPS-induced decreases in circulating IGF-I and IGFBP-3 and their gene expression in the liver Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E50 - E56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Kimball, R. A. Orellana, P. M. J. O'Connor, A. Suryawan, J. A. Bush, H. V. Nguyen, M. C. Thivierge, L. S. Jefferson, and T. A. Davis Endotoxin induces differential regulation of mTOR-dependent signaling in skeletal muscle and liver of neonatal pigs Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E637 - E644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Fernandez-Celemin, N. Pasko, V. Blomart, and J.-P. Thissen Inhibition of muscle insulin-like growth factor I expression by tumor necrosis factor-alpha Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1279 - E1290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Orellana, P. M. J. O'Connor, H. V. Nguyen, J. A. Bush, A. Suryawan, M. C. Thivierge, M. L. Fiorotto, and T. A. Davis Endotoxemia reduces skeletal muscle protein synthesis in neonates Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E909 - E916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sugita, M. Kaneki, E. Tokunaga, M. Sugita, C. Koike, S. Yasuhara, R. G. Tompkins, and J. A. J. Martyn Inducible nitric oxide synthase plays a role in LPS-induced hyperglycemia and insulin resistance Am J Physiol Endocrinol Metab, February 1, 2002; 282(2): E386 - E394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Lang, G. J. Nystrom, and R. A. Frost Burn-induced changes in IGF-I and IGF-binding proteins are partially glucocorticoid dependent Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2002; 282(1): R207 - R215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Fedele, C. H. Lang, and P. A. Farrell Immunization against IGF-I prevents increases in protein synthesis in diabetic rats after resistance exercise Am J Physiol Endocrinol Metab, June 1, 2001; 280(6): E877 - E885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Lang, R. A. Frost, A. C. Nairn, D. A. MacLean, and T. C. Vary TNF-alpha impairs heart and skeletal muscle protein synthesis by altering translation initiation Am J Physiol Endocrinol Metab, February 1, 2002; 282(2): E336 - E347. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
