Hsp27 inhibits IKKβ-induced NF-κB activity and skeletal muscle atrophy
Hsp27 inhibits IKKβ-induced NF-κB activity and skeletal muscle atrophy
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DOI：
10.1096/fj.08-124602
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Judge, Andrew R.
中科院分区：
文献类型：
--
作者：
Dodd, Stephen L.;Hain, Brian;Judge, Andrew R.
热休克蛋白25/27（Heat shock protein 25/27，Hsp 25/27）是一种细胞保护蛋白，广泛存在于大多数细胞中，在细胞应激时表达上调。先前在非肌肉细胞中的研究表明，Hsp 27抑制TNF-α诱导的NF-κ B活化。在骨骼肌废用过程中，HSP 25/27水平降低，NF-κ B活性增加，而NF-κ B活性的这种增加是废用性肌肉萎缩所必需的。因此，本研究的目的是确定在骨骼肌废用之前，将HSP 27电转移到大鼠比目鱼肌中是否足以抑制骨骼肌废用性萎缩和NF-κ B激活。在未转染的纤维中观察到的35%废用性肌纤维萎缩在用Hsp 27转染的纤维中减弱了50%。热休克蛋白27也抑制废用诱导的增加MuRF 1和atrogin-1转录的82%和40%，分别。此外，废用和IKK β诱导的NF-κ B反式激活被Hsp 27消除。相反，Hsp 27对Foxo反式激活没有影响。总之，Hsp 27是体内骨骼肌中NF-κ B的负调节剂，并且足以抑制MuRF 1和atrogin-1并减轻骨骼肌废用性萎缩。Dodd，S. L.，海恩，B.，Senf，S. M.，Judge，A. R.热休克蛋白27抑制IKK β诱导的NF-κ B活性和骨骼肌萎缩。FASEB J.23，3415-3423（2009）. www.fasebj.org
Heat shock protein 25/27 (Hsp25/27) is a cytoprotective protein that is ubiquitously expressed in most cells, and is up-regulated in response to cellular stress. Previous work, in nonmuscle cells, has shown that Hsp27 inhibits TNF-alpha-induced NF-kappa B activation. During skeletal muscle disuse, Hsp25/27 levels are decreased and NF-kappa B activity increased, and this increase in NF-kappa B activity is required for disuse muscle atrophy. Therefore, the purpose of the current study was to determine whether electrotransfer of Hsp27 into the soleus muscle of rats, prior to skeletal muscle disuse, is sufficient to inhibit skeletal muscle disuse atrophy and NF-kappa B activation. The 35% disuse muscle-fiber atrophy observed in nontransfected fibers was attenuated by 50% in fibers transfected with Hsp27. Hsp27 also inhibited the disuse-induced increase in MuRF1 and atrogin-1 transcription by 82 and 40%, respectively. Furthermore, disuse- and IKK beta-induced NF-kappa B transactivation were abolished by Hsp27. In contrast, Hsp27 had no effect on Foxo transactivation. In conclusion, Hsp27 is a negative regulator of NF-kappa B in skeletal muscle, in vivo, and is sufficient to inhibit MuRF1 and atrogin-1 and attenuate skeletal muscle disuse atrophy.-Dodd, S. L., Hain, B., Senf, S. M., Judge, A. R. Hsp27 inhibits IKK beta-induced NF-kappa B activity and skeletal muscle atrophy. FASEB J. 23, 3415-3423 ( 2009). www.fasebj.org