Document Detail


Sirt1 increases skeletal muscle precursor cell proliferation.
MedLine Citation:
PMID:  18922599     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It is important to understand the mechanisms that control muscle precursor cell (MPC) proliferation for the development of countermeasures to offset the deleterious effects of the aging-related loss of skeletal muscle mass (and myonuclei) and the impaired ability of old muscle to regrow and regenerate. Over-expression of the NAD+-dependent histone deacetylase Sirt1 increased MPC proliferation and cell cycle progression as evidenced by increased 5-bromo-2'-deoxyuridine (BrdU) incorporation, an increase in cell number, proliferating cell nuclear antigen expression, and the phosphorylation of retinoblastoma protein. Associated with the Sirt1-mediated increase in MPC cycle progression were the bidirectional decreases and increases in the expression of the cyclin-dependent kinase inhibitors p21(Waf/Cip1) and p27(Kip1), respectively. Based upon our recent observation that lowering oxygen (O2) in culture from ambient (20%) to estimated physiological levels (5%) increased MPC proliferation, we next measured Sirt1 protein at 5% and 20% O2. Interestingly, in addition to increased proliferation in MPCs cultured at 5% O2, Sirt1 expression increased, compared to 20% O2. Using O2 levels as a platform to modulate basal Sirt1 protein, activation of Sirt1 activity with resveratrol in 20% O2 increased MPC proliferation while inhibition of Sirt1 with nicotinamide in 5% O2 lowered proliferation. For the first time, Sirt1 has been shown to increase MPC proliferation. These findings could have clinical significance since MPC proliferation has important implications in regulating skeletal muscle growth, maintenance, and repair, and the aging-related loss of skeletal muscle mass.
Authors:
Christopher R Rathbone; Frank W Booth; Simon J Lees
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-10-14
Journal Detail:
Title:  European journal of cell biology     Volume:  88     ISSN:  1618-1298     ISO Abbreviation:  Eur. J. Cell Biol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-02-19     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  7906240     Medline TA:  Eur J Cell Biol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  35-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics,  metabolism
Animals
Biological Markers / metabolism
Cell Proliferation*
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21 / genetics,  metabolism
Cyclin-Dependent Kinase Inhibitor p27 / genetics,  metabolism
Flow Cytometry
Humans
Male
Mice
Muscle, Skeletal / cytology*
Oxygen / metabolism
Rats
Sirtuin 1
Sirtuins / genetics,  metabolism*
Stem Cells / cytology,  physiology*
Grant Support
ID/Acronym/Agency:
AG18780/AG/NIA NIH HHS; AR048523/AR/NIAMS NIH HHS; R01 AG018780-08/AG/NIA NIH HHS; T32 AR048523/AR/NIAMS NIH HHS; T32 AR048523-05/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cyclin-Dependent Kinase Inhibitor p21; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 3.5.1.-/Sirt1 protein, mouse; EC 3.5.1.-/Sirt1 protein, rat; EC 3.5.1.-/Sirtuin 1; EC 3.5.1.-/Sirtuins; S88TT14065/Oxygen
Comments/Corrections

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


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