Document Detail


Response of the ubiquitin-proteasome pathway to changes in muscle activity.
MedLine Citation:
PMID:  15886351     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The ubiquitin-proteasome pathway plays a critical role in the adaptation of skeletal muscle to persistent decreases or increases in muscle activity. This article outlines the basics of pathway function and reviews what we know about pathway responses to altered muscle use. The ubiquitin-proteasome pathway regulates proteolysis in mammalian cells by attaching ubiquitin polymers to damaged proteins; this targets the protein for degradation via the 26S proteasome. The pathway is constitutively active in muscle and continually regulates protein turnover. Conditions of decreased muscle use, e.g., unloading, denervation, or immobilization, stimulate general pathway activity. This activity increase is caused by upregulation of regulatory components in the pathway and leads to accelerated proteolysis, resulting in net loss of muscle protein. Pathway activity is also increased in response to exercise, a two-phase response. An immediate increase in selective ubiquitin conjugation by constitutive pathway components contributes to exercise-stimulated signal transduction. Over hours-to-days, exercise also stimulates a delayed increase in general ubiquitin conjugating activity by inducing expression of key components in the pathway. This increase mediates a late-phase rise in protein degradation that is required for muscle adaptation to exercise. Thus the ubiquitin-proteasome pathway functions as an essential mediator of muscle remodeling, both in atrophic states and exercise training.
Authors:
Michael B Reid
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  288     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-11     Completed Date:  2005-06-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1423-31     Citation Subset:  IM; S    
Affiliation:
Department of Physiology, University of Kentucky, 800 Rose St., Rm. MS-509, Lexington, KY 40536-0298, USA. michael.reid@uky.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Humans
Muscle, Skeletal / physiology*
Proteasome Endopeptidase Complex / physiology*
Signal Transduction / physiology*
Ubiquitin / physiology*
Grant Support
ID/Acronym/Agency:
HL-59878/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Ubiquitin; EC 3.4.25.1/Proteasome Endopeptidase Complex
Investigator
Investigator/Affiliation:
M B Reid / U KY, Lexington

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Metabolism of verapamil in cultures of rat alveolar epithelial cells and pharmacokinetics after admi...
Next Document:  Adrenomedullin: angiogenesis and gene therapy.