Increased nitric oxide synthase activity and Hsp90 association in skeletal muscle following chronic exercise.

Increased nitric oxide synthase activity and Hsp90 association in skeletal muscle following chronic exercise.
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DOI:
10.1007/s00421-008-0833-4
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发表时间:
2008-11
影响因子:
3
通讯作者:
Venema RC
Venema RC
中科院分区:
医学3区
文献类型:
--
作者:
Harris MB;Mitchell BM;Sood SG;Webb RC;Venema RC

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运动训练会导致骨骼肌血流和新陈代谢的动态变化。一氧化氮 (NO) 影响血流、氧化应激和葡萄糖代谢。 Hsp90 直接与一氧化氮合酶 (NOS) 相互作用,增加 NOS 活性并改变超氧化物与 NO 产生的平衡。此外,运动后各种组织中 Hsp90 的表达也会增加。因此,我们测试了运动训练增加骨骼肌中 Hsp90 表达以及 Hsp90/NOS 关联和 NOS 活性的假设。雄性 Sprague-Dawley 大鼠被分配到久坐组或运动训练组(n=10/组)。运动训练包括在电动跑步机上以 30 m/min、5% 坡度跑步 1 小时,持续 10 周。蛋白质印迹显示,运动训练导致比目鱼肌中 Hsp90 表达增加 1.9±0.1 倍,但 nNOS、iNOS 或 eNOS 没有增加。运动训练还导致 Hsp90 与 nNOS 的关联增加 3.4+1.0 倍,通过免疫沉淀测量与 eNOS 的关联增加 2.3±0.4 倍,以及 eNOS Ser-1179 磷酸化增加 1.5±0.3 倍。与对照组相比,运动训练后比目鱼肌中通过[14C]-L-精氨酸转化为[14C]-L-瓜氨酸的转化率测量的总NOS活性增加了1.42±0.9倍。总之,大鼠为期 10 周的跑步机训练计划导致比目鱼肌中总 NOS 活性显着增加,部分原因可能是 NOS 与 Hsp90 和磷酸化的相互作用增加。这种相互作用可能在改变肌肉血流量和骨骼肌氧化还原状态中发挥作用。
Exercise training results in dynamic changes in skeletal muscle blood flow and metabolism. Nitric oxide (NO) influences blood flow, oxidative stress, and glucose metabolism. Hsp90 interacts directly with nitric oxide synthases (NOS), increasing NOS activity and altering the balance of superoxide versus NO production. In addition, Hsp90 expression increases in various tissues following exercise. Therefore, we tested the hypothesis that exercise training increases Hsp90 expression as well as Hsp90/NOS association and NOS activity in skeletal muscle. Male, Sprague-Dawley rats were assigned to either a sedentary or exercise trained group (n=10/group). Exercise training consisted of running on a motorized treadmill for 10 weeks at 30 m/min, 5% grade for 1 h. Western blotting revealed that exercise training resulted in a 1.9±0.1-fold increase in Hsp90 expression in the soleus muscle but no increase in nNOS, iNOS, or eNOS. Exercise training also resulted in a 3.4+1.0 fold increase in Hsp90 association with nNOS, a 2.3±0.4-fold increase association with eNOS measured by immunoprecipitation as well as a 1.5±0.3-fold increase in eNOS phosphorylation at Ser-1179. Total NOS activity measured by the rate of conversion of [14C]-L-arginine to [14C]-L-citrulline was increased by 1.42±0.9-fold in soleus muscle following exercise training compared to controls. In summary, a 10-week treadmill training program in rats results in a significant increase in total NOS activity in the soleus which may be due, in part, to increased NOS interaction with Hsp90 and phosphorylation. This interaction may play a role in altering muscle blood flow and skeletal muscle redox status.
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