Department of Orthopedics, the Second Hospital, Shanxi Medical University, Taiyuan, China.
Braz J Med Biol Res. 2012 Aug;45(8):711-5. doi: 10.1590/s0100-879x2012007500080. Epub 2012 May 17.
Activated inhibitor of nuclear factor-κB kinase β (IKKβ) is necessary and sufficient for denervated skeletal muscle atrophy. Although several studies have shown that Mg(2+)/Mn(2+)-dependent protein phosphatase 1B (PPM1B) inactivated IKKβ, few studies have investigated the role of PPM1B in denervated skeletal muscle. In this study, we aim to explore the expression and significance of PPM1B and phosphorylated IKKβ (P-IKKβ) during atrophy of the denervated gastrocnemius. Thirty young adult female Wistar rats were subjected to right sciatic nerve transection and were sacrificed at 0 (control), 2, 7, 14, and 28 days after denervation surgery. The gastrocnemius was removed from both the denervated and the contralateral limb. The muscle wet weight ratio was calculated as the ratio of the wet weight of the denervated gastrocnemius to that of the contralateral gastrocnemius. RT-PCR and Western blot analysis showed that mRNA and protein levels of PPM1B were significantly lower than those of the control group at different times after the initiation of denervation, while P-IKKβ showed the opposite trends. PPM1B protein expression persistently decreased while P-IKKβ expression persistently increased for 28 days after denervation. PPM1B expression correlated negatively with P-IKKβ expression by the Spearman test, whereas decreasing PPM1B expression correlated positively with the muscle wet weight ratio. The expression levels of PPM1B and P-IKKβ were closely associated with atrophy in skeletal denervated muscle. These results suggest that PPM1B and P-IKKβ could be markers in skeletal muscle atrophy.
激活核因子-κB 激酶β（IKKβ）抑制剂对于失神经骨骼肌萎缩是必要且充分的。尽管有几项研究表明，Mg2+/Mn2+依赖性蛋白磷酸酶 1B（PPM1B）可使 IKKβ失活，但很少有研究探讨 PPM1B 在失神经骨骼肌中的作用。在这项研究中，我们旨在探讨 PPM1B 和磷酸化 IKKβ（P-IKKβ）在失神经腓肠肌萎缩过程中的表达和意义。30 只年轻成年雌性 Wistar 大鼠接受右侧坐骨神经切断术，并在术后 0（对照）、2、7、14 和 28 天处死。从失神经和对侧腓肠肌中取出腓肠肌。肌湿重比计算为失神经腓肠肌湿重与对侧腓肠肌湿重的比值。RT-PCR 和 Western blot 分析显示，失神经后不同时间点 PPM1B 的 mRNA 和蛋白水平均明显低于对照组，而 P-IKKβ则呈现相反的趋势。PPM1B 蛋白表达持续下降，而 P-IKKβ 表达持续增加，直至失神经后 28 天。PPM1B 表达与 P-IKKβ表达呈负相关，Spearman 检验；而 PPM1B 表达降低与肌肉湿重比呈正相关。PPM1B 和 P-IKKβ 的表达水平与骨骼肌失神经萎缩密切相关。这些结果表明，PPM1B 和 P-IKKβ 可能是骨骼肌萎缩的标志物。
