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The effects of PGC-1alpha on control of micro vascular P_(O_2) kinetics following onset of muscle contractions

机译:PGC-1αbo对肌肉收缩发作后微血管P_(O_2)动力学控制的影响

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During contractions, regulation of microvascular oxygen partial pressure (Pmvo_2), which drives blood-myocyte O_2 flux, is a function of skeletal muscle fiber type and oxidative capacity and can be altered by exercise training. The kinetics of Pmvo_2 during contractions in predominantly fast-twitch muscles evinces a more rapid fall to far lower levels compared with slow-twitch counterparts. Peroxisome prolifera-tor-activated receptor 7 coactivator la (PGC-1alpha) 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-1alpha would be associated with an altered Pmvo_2 kinetics 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 Pmvo_2). Phosphorescence quenching techniques were used to measure Pmvo_2 at rest and during separate bouts of twitch (1 Hz) and tetanic (100 Hz) contractions in gastrocnemius muscles of mice with overexpression of PGC-1alpha and wild-type littermates (WT) mice under isoflurane anesthesia. Muscles of PGC-1alpha mice exhibited less fatigue than WT (P < 0.01). However, except for the Pmvo_2 response immediately following onset of contractions, WT and PGC-1alpha mice demonstrated similar Pmvo_2 kinetics. Specifically, the time delay of the Pmvo_2 response was shortened in PGC-1alpha mice compared with WT (1 Hz: WT, 6.6 ± 2.4 s; PGC-1alpha, 2.9 ± 0.8 s; 100 Hz: WT, 3.3 ± 1.1 s, PGC-1alpha, 0.9 ± 0.3 s, both P < 0.05). The ratio of muscle force to Pmvo_2 was higher for the duration of tetanic contractions in PGC-1alpha mice. Slower dynamics and maintenance of higher Pmvo_2 following muscle contractions is not obligatory for improved fatigue resistance in fast-twitch muscle of PGC-1alpha mice. Moreover, overexpression of PGC-1alpha may accelerate O_2 utilization kinetics to a greater extent than O_2 delivery kinetics.
机译:在收缩期间,传动血液肌细胞O_2通量的微血管氧分压(PMVO_2)的调节是骨骼肌纤维型和氧化能力的函数,并且可以通过运动训练改变。与慢速分布的同行相比,在收缩期间PMVO_2在收缩期间的动力学表现出更快的速度下降到远低。过氧化物组织增殖 - 激活受体7共诱变剂LA(PGC-1α)可提高耐久性,部分原因是由于线粒体生物发生,纤维型开关与氧化纤维,骨骼肌中的血管生成。我们测试了假设,即通过PGC-1α的遗传过表达改善运动能力的改善将与在慢速抽搐肌肉(即,慢速动力学减慢的响应动力学中)的收缩期间快速抽搐(白色)胃肠内半月的改变的PMVO_2动力学曲线相关联。和升高的稳态PMVO_2)。磷光猝灭技术用于测量休息的PMVO_2,在小鼠的胃肠杆菌肌肉中的胃肠杆菌肌肉中的分开(1Hz)和滴注(100Hz)收缩期间测量pGC-1αb和野生型枯萎病(WT)小鼠在异氟烷麻醉下。 PGC-1Alpha小鼠的肌肉表现出比wt更小的疲劳(P <0.01)。然而,除了收缩发作后立即进行PMVO_2响应,WT和PGC-1Alpha小鼠展示了类似的PMVO_2动力学。具体地,与WT(1Hz:WT,6.6±2.4 S; PGC-1Alpha,2.9±0.8 S; 100Hz:WT,3.3±1.1 S,PGC-1,6.6±2.4 S; 100 Hz:WT,3.3±1.1 S,PGC,缩短了PGC-1α响应的时间延迟。 -1Alpha,0.9±0.3秒,P <0.05)。对于PGC-1α小鼠的滴答物收缩的持续时间,肌肉力与PMVO_2的比率更高。肌肉收缩后较高PMVO_2的较慢动态和维持较慢的动力学和维持不义务改善PGC-1α小鼠的快速抽搐肌肉中的抗疲劳性。此外,PGC-1α的过度表达可以在更大程度上加速O_2利用动力学,而不是O_2递送动力学。

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