Sirt1 increases skeletal muscle precursor cell proliferation.
Sirt1 increases skeletal muscle precursor cell proliferation.
复制标题
SIRT1增加骨骼肌前体细胞增殖。
DOI：
10.1016/j.ejcb.2008.08.003
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发表时间：
2009-01
影响因子：
6.6
通讯作者：
Lees, Simon J.
中科院分区：
文献类型：
--
作者：
Rathbone, Christopher R.;Booth, Frank W.;Lees, Simon J.
了解控制肌肉前体细胞（MPC）增殖的机制对于开发对抗措施以抵消与衰老相关的骨骼肌质量（和肌核）损失和旧肌肉再生和再生能力受损的有害影响是重要的。NAD+依赖性组蛋白去乙酰化酶Sirt 1的过度表达增加MPC增殖和细胞周期进展，如5-溴-2 ′-脱氧尿苷（BrdU）掺入增加、细胞数量增加、增殖细胞核抗原表达和视网膜母细胞瘤蛋白磷酸化。与Sirt 1介导的MPC周期进展增加相关的是细胞周期蛋白依赖性激酶抑制剂p21 Waf/Cip 1和p27 Kip 1表达的双向减少和增加。基于我们最近的观察，即将培养物中的氧气（O2）从环境（20%）降低到估计的生理水平（5%）增加了MPC增殖，我们接下来在5%和20%O2下测量了Sirt 1蛋白。有趣的是，除了在5%O2下培养的MPC中增殖增加外，与20%O2相比，Sirt 1表达增加。使用O2水平作为一个平台，以调节基础Sirt 1蛋白，激活Sirt 1活性与白藜芦醇在20%O2增加MPC增殖，而抑制Sirt 1与烟酰胺在5%O2降低增殖。Sirt 1首次被证明可以增加MPC的增殖。这些发现可能具有临床意义，因为MPC增殖在调节骨骼肌生长、维持和修复以及骨骼肌质量的老化相关损失中具有重要意义。
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.
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影响因子：
10.5
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通讯作者：
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