Chronic treatment with agents that stabilize cytosolic IκB-α enhances survival and improves resting membrane potential in MDX muscle fibers subjected to chronic passive stretch
Chronic treatment with agents that stabilize cytosolic IκB-α enhances survival and improves resting membrane potential in MDX muscle fibers subjected to chronic passive stretch
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DOI：
10.1016/j.nbd.2005.05.003
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发表时间：
2005-12-01
影响因子：
6.1
通讯作者：
Siegel, A
中科院分区：
文献类型：
--
作者：
Carlson, CG;Samadi, A;Siegel, A
通过用稳定胞质I kappa B-α（x）（吡咯烷二硫代氨基甲酸酯，PDTC）的药物治疗成年mdx小鼠，并检查这种治疗对慢性拉伸的mdx小鼠胸骨三角肌（TS）肌肉的影响，检查了被动拉伸营养不良骨骼肌中NF kappa B信号传导增加的潜在致病作用。每日PDTC治疗显著增加了存活的纹状TS纤维的数量，而与年龄无关。来自未处理mdx小鼠的TS纤维的静息电位（RP）显著低于非营养不良小鼠。用GdCl 3阻断静息Ca 2+内流的治疗对非营养不良或mdx制剂中的RP没有影响。每天用PDTC治疗显著改善RP，与年龄无关。这些结果与被动牵拉激活营养不良肌肉中NF κ B介导的致病机制的假设一致，并表明稳定胞质I κ B-α水平的试剂可用于治疗杜氏肌营养不良和相关的肌营养不良。(c)2005年爱思唯尔公司All rights reserved.
The potential pathogenic role of increased NF kappa B signaling in passively stretched dystrophic skeletal muscle was examined by treating adult mdx mice with an agent that stabilized cytosolic I kappa B-alpha(x (pyrollidine dithiocarbamate, PDTC)and examining the effects of this treatment on the chronically stretched mdx triangularis sterni (TS) muscle. Daily PDTC treatment significantly increased the number of surviving striated TS fibers regardless of age. TS fibers from untreated mdx mice had significantly lower resting potentials (RPs) than nondystrophic mice. Treatment with GdCl3 to block resting Ca2+ influx had no effect on RP in either nondystrophic or mdx preparations. Daily treatment with PDTC significantly improved the RP regardless of age. These results are consistent with the hypothesis that passive stretch activates an NF kappa B-mediated pathogenic mechanism in dystrophic muscle and suggest that agents which stabilize cytosolic l kappa B-alpha levels may be useful for treating Duchenne and related muscular dystrophies. (c) 2005 Elsevier Inc. All rights reserved.