| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print July 30, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00181.2002
Submitted on April 29, 2002
Accepted on July 11, 2002
1 Departments of Cellular and Molecular Physiology and Surgery, Pennsylvania State College of Medicine, Hershey, PA, USA
* To whom correspondence should be addressed. E-mail: clang{at}psu.edu.
Alcoholic myopathy is a relatively common occurrence the etiology of which is incompletely understood. The purpose of the present study was to determine whether acute alcohol (ETOH) intoxication in rats impaired components of the insulin and IGF-I signaling pathway in skeletal muscle. Rats were injected intraperitoneally with 75 mmol/Kg of ETOH or an equal volume of saline. After 2.5 h, either insulin, IGF-I or saline was injected intravenously and the gastrocnemius was removed at 2 min or 20 min. Acute ETOH intoxication did not alter the total amount or tyrosine phosphorylation of the insulin receptor, IGF-I receptor, IRS-1, or PKB/Akt under basal or hormone-stimulated conditions. In contrast, ETOH attenuated the ability of insulin to stimulate phosphorylation of ribosomal S6 kinase (S6K)-1 on both the T389 residue (~65%) and T421/S424 residue (~50%). Furthermore, ETOH completely prevented the phosphorylation of these residues by IGF-I. Alcohol-induced inhibition of S6K1 was associated with a reduction in the phosphorylation of the ribosomal protein S6. Under basal conditions, ETOH altered the distribution of eukaryotic initiation factor (eIF) 4E, as evidenced by a decreased amount of the active eIF4E [[bull1]]eIF4G complex (~60%), an increased amount of inactive eIF4E[[bull1]]4E-BP1 complex (75-125%), and decreased phosphorylation of 4E-BP1 (~40%). In contrast, ETOH did not impair the ability of either insulin or IGF-I to reverse the above mentioned changes in eIF4E distribution and 4E-BP1 phosphorylation. Previous studies have shown that acute alcohol intoxication enhances endogenous glucocorticoid secretion and that synthetic glucocorticoids impair mRNA translation. However, pretreatment of rats with the glucocorticoid receptor antagonist RU486 was unable to prevent or attenuate either the basal ETOH-induced changes in eIF4E distribution or the impaired ability of IGF-I to stimulated S6K1 and S6 phosphorylation. Hence, acute alcohol intoxication alters selected aspects of translational control under both basal and anabolic hormone-stimulated conditions in skeletal muscle in a glucocorticoid-independent manner.
This article has been cited by other articles:
|
|
 |
|
  Q. Jiao, A. M. Pruznak, D. Huber, T. C. Vary, and C. H. Lang Castration differentially alters basal and leucine-stimulated tissue protein synthesis in skeletal muscle and adipose tissue Am J Physiol Endocrinol Metab, November 1, 2009; 297(5): E1222 - E1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Lang Elevated plasma free fatty acids decrease basal protein synthesis, but not the anabolic effect of leucine, in skeletal muscle Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E666 - E674. [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]
|
|
|
|
 |
|
 L. Q. Hong-Brown, C. R. Brown, and C. H. Lang Indinavir impairs protein synthesis and phosphorylations of MAPKs in mouse C2C12 myocytes Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1482 - C1492. [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, E. Svanberg, and T. C. Vary IGF-I/IGFBP-3 ameliorates alterations in protein synthesis, eIF4E availability, and myostatin in alcohol-fed rats Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E916 - E926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Lang, R. A. Frost, N. Deshpande, V. Kumar, T. C. Vary, L. S. Jefferson, and S. R. Kimball Alcohol impairs leucine-mediated phosphorylation of 4E-BP1, S6K1, eIF4G, and mTOR in skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2003; 285(6): E1205 - E1215. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
