Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia
Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia
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DOI：
10.1007/s10038-006-0397-2
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发表时间：
2006-06-01
影响因子：
3.5
通讯作者：
Ueno, Satoshi
中科院分区：
文献类型：
--
作者：
Kin, Tesseki;Sugie, Kazuma;Ueno, Satoshi
我们发现，humanin（HN），一种内源性肽对阿尔茨海默病相关的侮辱，表达在慢性进行性眼外肌麻痹（CPEO），一种主要的线粒体疾病患者的肌肉。由于HN最近被发现阻断促凋亡Bax功能，并发挥其多功能的细胞保护作用与ATP水平的增加，HN的表达，因此可能反映了对CPEO患者的肌肉退行性变化的生理反应。我们发现HN表达在所有四名患者检查，每个人都有不同的线粒体DNA突变，包括两个不同的单DNA缺失，多个缺失，没有检测到重大突变。我们还发现，HN表达与局灶性细胞色素c缺乏症无关，与单缺失CPEO亚型密切相关。这些结果表明，HN表达更密切相关的退行性变化，在所有类型的CPEO。值得注意的是，HN也在CPEO或Leigh综合征患者的非变性肌纤维中表达，这些患者在线粒体ATP酶6基因中具有已知与ATP合成受损相关的8993T > G突变。总的来说，我们的研究结果表明，HN可能是特异性表达的线粒体异常的肌肉中的能量生产缺陷。
We showed that humanin (HN), an endogenous peptide against Alzheimer disease-related insults, was expressed in muscles of patients with chronic progressive external ophthalmoplegia (CPEO), a major mitochondrial disease. Because HN was recently found to block proapoptotic Bax function and exert its versatile cytoprotective effects in association with an increase in ATP levels, HN expression may thus reflect a physiological response against degenerative changes in the muscles of patients with CPEO. We found HN expression in all four patients examined, each of whom had different mitochondrial DNA mutations including two different single DNA deletions, multiple deletions, and no major mutations detected. We also found that HN expression was not linked to focal cytochrome c deficiency, strongly associated with the subtype of CPEO with single deletions. These results suggest that HN expression is more closely related to degenerative changes in all types of CPEO. Notably, HN was also expressed in non-degenerative muscle fibers of patients with CPEO or Leigh syndrome, who had the 8993T > G mutation in the mitochondrial ATPase 6 gene known to be associated with impaired ATP synthesis. Collectively, our findings suggest that HN may be specifically expressed in response to defects in energy production in muscles with mitochondrial abnormalities.