NDLI: Sirt1 increases skeletal muscle precursor cell proliferation

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Sirt1 increases skeletal muscle precursor cell proliferation

Content Provider	PubMed Central
Author	Rathbone, Christopher R. Booth, Frank W. Lees, Simon J.
Abstract	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 Sirt1-mediated increase in MPC cycle progression were the bidirectional decreases and increases in the expression of the cyclin-dependent kinase inhibitors p21Waf/Cip1 and p27Kip1, 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.
Related Links	http://dx.doi.org/10.1016/j.ejcb.2008.08.003
Ending Page	44
Page Count	10
Starting Page	35
File Format	PDF
ISSN	01719335
e-ISSN	16181298
Journal	European journal of cell biology
Issue Number	1
Volume Number	88
Language	English
Publisher Date	2009-01-01
Access Restriction	Open
Subject Keyword	Pathology and Forensic Medicine Cell Biology Histology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Histology Pathology and Forensic Medicine

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