The effects of PGC-1α on control of microvascular P(O2) kinetics following onset of muscle contractions.
The effects of PGC-1α on control of microvascular P(O2) kinetics following onset of muscle contractions.
复制标题
PGC-1α 对肌肉收缩开始后微血管 P(O2) 动力学控制的影响。
DOI：
10.1152/japplphysiol.00080.2014
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发表时间：
2014
期刊：
影响因子：
3.3
通讯作者：
Poole DC.
中科院分区：
文献类型：
--
作者：
Kano Y;Miura S;Eshima H;Ezaki O;Poole DC.
在收缩过程中，微血管氧分压(Pmvo2)的调节是骨骼肌纤维类型和氧化能力的函数，运动训练可以改变这种调节。在以快抽动为主的肌肉收缩过程中，Pmvo2的动力学表现出比慢抽动肌肉更快地下降到远低于慢抽动肌肉的水平。过氧化物酶体增殖物激活受体γ辅活化子1α(PGC-1α)可提高耐力能力，部分原因是由于线粒体的生物生成，一种纤维型氧化纤维的转换，以及骨骼肌中的血管生成。我们测试了这样一种假设，即通过遗传过量表达PGC-1α来提高运动能力将与快抽动(白色)腓肠肌在收缩过程中Pmvo2动力学曲线的改变有关(即，反应动力学减慢和稳态Pmvo2升高)。用磷光猝灭技术测定异氟醚麻醉下pGC-1α高表达小鼠和野生型小鼠(WT)腓肠肌在静息状态、抽动(1 Hz)和强直(100 Hz)收缩时的Pmvo2。PGC-1α小鼠肌肉疲劳程度低于WT小鼠(P<；0.01)。然而，除了在收缩开始后立即出现Pmvo2反应外，WT和pGC-1α小鼠表现出相似的Pmvo2动力学。PGC-1α小鼠Pmvo2反应的时间延迟明显短于wt(1赫兹：WT，6.6±2.4 S；pGC-1α，2.9±0.8 S；100 Hz：WT，3.3±1.1 S，pGC-1α，0.9±0.3 S，均P<；0.05)。在强直性收缩持续时间内，pGC-1α小鼠的肌力与Pmvo2的比值较高。肌肉收缩后较慢的动力学和维持较高的Pmvo2并不是提高pGC-1α小鼠快速抽动肌肉抗疲劳能力的必要条件。此外，PGC-1α的过表达可能在更大程度上加速了O2的利用动力学，而不是O2的输送动力学。
During contractions, regulation of microvascular oxygen partial pressure (Pmvo2), which drives blood-myocyte O2flux, is a function of skeletal muscle fiber type and oxidative capacity and can be altered by exercise training. The kinetics of Pmvo2during contractions in predominantly fast-twitch muscles evinces a more rapid fall to far lower levels compared with slow-twitch counterparts. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) improves endurance performance, in part, due to mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. We tested the hypothesis that improvement of exercise capacity by genetic overexpression of PGC-1α would be associated with an altered Pmvo2kinetics profile of the fast-twitch (white) gastrocnemius during contractions toward that seen in slow-twitch muscles (i.e., slowed response kinetics and elevated steady-state Pmvo2). Phosphorescence quenching techniques were used to measure Pmvo2at rest and during separate bouts of twitch (1 Hz) and tetanic (100 Hz) contractions in gastrocnemius muscles of mice with overexpression of PGC-1α and wild-type littermates (WT) mice under isoflurane anesthesia. Muscles of PGC-1α mice exhibited less fatigue than WT (P< 0.01). However, except for the Pmvo2response immediately following onset of contractions, WT and PGC-1α mice demonstrated similar Pmvo2kinetics. Specifically, the time delay of the Pmvo2response was shortened in PGC-1α mice compared with WT (1 Hz: WT, 6.6 ± 2.4 s; PGC-1α, 2.9 ± 0.8 s; 100 Hz: WT, 3.3 ± 1.1 s, PGC-1α, 0.9 ± 0.3 s, bothP< 0.05). The ratio of muscle force to Pmvo2was higher for the duration of tetanic contractions in PGC-1α mice. Slower dynamics and maintenance of higher Pmvo2following muscle contractions is not obligatory for improved fatigue resistance in fast-twitch muscle of PGC-1α mice. Moreover, overexpression of PGC-1α may accelerate O2utilization kinetics to a greater extent than O2delivery kinetics.