Acute exercise activates nuclear factor (NF)-κB signaling pathway in rat skeletal muscle
Acute exercise activates nuclear factor (NF)-κB signaling pathway in rat skeletal muscle
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DOI：
10.1096/fj.04-1846com
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发表时间：
2004-10-01
期刊：
影响因子：
4.8
通讯作者：
Vina, J
中科院分区：
文献类型：
--
作者：
Ji, LL;Gomez-Cabrera, MC;Vina, J
本研究通过两项实验探讨了急性运动对大鼠骨骼肌核蛋白kappaB（NF-κ B）信号通路的影响。在研究1中，一组大鼠（n = 6）在跑步机上以25 m/min、5%的速度跑步1小时或直至精疲力尽（Ex），并与注射两剂吡咯烷二硫代氨基甲酸酯（PDTC，100 mg/kg，腹腔注射）的第二组（n = 6）进行比较。急性运动前24和1 h。另外三组大鼠（n = 6）用8 mg/kg（i. p.）脂多糖（LPS），lmmol/kg（i. p.）叔丁基过氧化氢（tBHP）或盐水（C），并在静止条件下杀死。与C组大鼠相比，Ex组大鼠肌核提取物中NF-κ B结合和P50蛋白含量水平较高。与对照组相比，细胞溶质IkappaB α和IkappaB激酶（IKK）含量降低，而磷酸化IkappaB α和磷酸化IKK含量升高。PDTC治疗可部分消除运动诱导的NF-κ B信号级联激活。LPS（而非tBHP）治疗模拟并夸大了在Ex大鼠中观察到的效应。在研究2中，检查了运动诱导的NF-κ B激活的时间过程。运动后2 h观察到最高水平的NF-κ B结合。运动后0 ~ 1 h，胞浆IkappaB α含量降低，磷酸化IkappaB α含量升高，而P65在2 ~ 4 h达到高峰。这些数据表明，NF-κ B信号通路可以在肌肉收缩期间以氧化还原敏感的方式被激活，推测是由于氧化剂产生增加。细胞内事件的级联可能是锰超氧化物歧化酶的基因表达升高的前奏（Pfluegers Arch.442，426 - 434，2001）。
Two studies were performed to investigate the effects of an acute bout of physical exercise on the nuclear protein kappaB (NF-kappaB) signaling pathway in rat skeletal muscle. In Study 1, a group of rats (n = 6) was run on the treadmill at 25 m/min, 5% grade, for 1 h or until exhaustion ( Ex), and compared with a second group ( n = 6) injected with two doses of pyrrolidine dithiocarbamate ( PDTC, 100 mg/kg, i.p.) 24 and 1 h prior to the acute exercise bout. Three additional groups of rats ( n = 6) were injected with either 8 mg/kg (i.p.) of lipopolysaccharide (LPS), 1 mmol/kg (i.p.) t-butylhydroperoxide (tBHP), or saline ( C) and killed at resting condition. Ex rats showed higher levels of NF-kappaB binding and P50 protein content in muscle nuclear extracts compared with C rats. Cytosolic IkappaBalpha and IkappaB kinase (IKK) contents were decreased, whereas phospho-IkappaBalpha and phospho-IKK contents were increased, comparing Ex vs. C. The exercise-induced activation of NF-kappaB signaling cascade was partially abolished by PDTC treatment. LPS, but not tBHP, treatment mimicked and exaggerated the effects observed in Ex rats. In Study 2, the time course of exercise-induced NF-kappaB activation was examined. Highest levels of NF-kappaB binding were observed at 2 h postexercise. Decreased cytosolic IkappaBalpha and increased phosphor-IkappaBalpha content were found 0 - 1 h postexercise whereas P65 reached peak levels at 2 - 4 h. These data suggest that the NF-kappaB signaling pathway can be activated in a redox-sensitive manner during muscular contraction, presumably due to increased oxidant production. The cascade of intracellular events may be the overture to elevated gene expression of manganese superoxide dismutase reported earlier Pfluegers Arch. 442, 426 - 434, 2001).