Redox Biology & Cell Signaling Laboratory, Department of Health and Kinesiology, Texas A&M University, College Station, TX 77843-4243, USA.
Med Sci Sports Exerc. 2012 Apr;44(4):600-9. doi: 10.1249/MSS.0b013e31823ab37a.
Extreme disuse and spaceflight elicit rapid skeletal muscle atrophy, accompanied by elevated proinflammatory signaling and impaired stress response proteins (e.g., heat shock proteins (HSP), insulin-like growth factor 1 (IGF-1)). Recovery of muscle mass is delayed during the early stage of reloading after prolonged unloading, with a concomitant impairment of HSP70 and IGF-1. We postulated that proinflammatory signaling and stress response alterations would characterize early and late phases of signaling during reloading.
Twenty-four adult SD rats were divided into the following groups: controls, 28 d of hind limb unloading (HU), HU + early (7 d) reloading (HU-R7), and HU + late (28 d) reloading (HU-R28).
Soleus mass decreased (-55%) with HU and remained depressed (-41%) at HU-R7. Nuclear factor κB activation and oxidative stress were elevated with HU and remained high during reloading. HU elevated inducible nitric oxide synthase and returned to baseline during reloading, whereas 3-nitrotyrosine did not increase with HU and peaked at HU-R7. HU depressed levels of HSP25 phosphorylation at Ser82 and IGF-1. Although p-HSP25 and Akt phosphorylation (Ser473) recovered during early reloading, HSP70, heat shock factor 1, and IGF-1 remained depressed. HSP70, heat shock factor 1, and IGF-1 recovered, whereas p-Akt and 3-nitrotyrosine decreased to control levels at HU-R28.
Reloading elicited an early phase characterized by elevated nuclear factor κB activation, 3-nitrotyrosine, p-HSP25, and p-Akt levels and a delayed phase with recovery of HSP70, IGF-1, and muscle mass. We conclude that the reloading phenotype in skeletal muscle is expressed in two distinct phases related to (a) pro-inflammatory signaling and (b) muscle mass recovery.
极度失用和太空飞行会引起骨骼肌迅速萎缩，伴随着促炎信号的增加和应激反应蛋白（如热休克蛋白（HSP）、胰岛素样生长因子 1（IGF-1））的受损。在长时间失用后的早期再加载阶段，肌肉质量的恢复会延迟，同时 HSP70 和 IGF-1 的功能也会受损。我们推测，在再加载过程中，促炎信号和应激反应的改变将是早期和晚期信号的特征。
将 24 只成年 SD 大鼠分为以下几组：对照组、28 天下肢去负荷（HU）组、HU+早期（7 天）再加载（HU-R7）组和 HU+晚期（28 天）再加载（HU-R28）组。
HU 使比目鱼肌质量减少（-55%），HU-R7 时仍保持抑制（-41%）。HU 时核因子 κB 激活和氧化应激增加，再加载时仍保持高水平。HU 时诱导型一氧化氮合酶增加，再加载时恢复正常，而 3-硝基酪氨酸（3-nitrotyrosine）与 HU 无关，在 HU-R7 时达到峰值。HU 降低 HSP25 磷酸化（Ser82）和 IGF-1 水平。尽管 p-HSP25 和 Akt 磷酸化（Ser473）在早期再加载时恢复，但 HSP70、热休克因子 1 和 IGF-1 仍处于抑制状态。HSP70、热休克因子 1 和 IGF-1 恢复，而 p-Akt 和 3-硝基酪氨酸（3-nitrotyrosine）降至 HU-R28 时的对照水平。
再加载引起了一个早期阶段，其特征是核因子 κB 激活、3-硝基酪氨酸、p-HSP25 和 p-Akt 水平升高，以及一个延迟阶段，表现为 HSP70、IGF-1 和肌肉质量的恢复。我们得出结论，骨骼肌的再加载表型表现为两个不同的阶段，与（a）促炎信号和（b）肌肉质量恢复有关。
