Humanin detected in skeletal muscles of MELAS patients: a possible new therapeutic agent
Humanin detected in skeletal muscles of MELAS patients: a possible new therapeutic agent
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DOI：
10.1007/s00401-004-0965-5
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发表时间：
2005-04-01
影响因子：
12.7
通讯作者：
Ueno, S
中科院分区：
文献类型：
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作者：
Kariya, S;Hirano, M;Ueno, S
Humanin（HN）最初被鉴定为保护神经细胞免受各种类型的阿尔茨海默病相关损伤诱导的凋亡的内源性肽。我们先前已经指出，HN增加细胞ATP水平，并推测这种肽可以拯救线粒体疾病中的能量缺乏细胞。在这里，我们报告，第一次，在骨骼肌线粒体脑肌病乳酸酸中毒和中风样发作（MELAS）患者的HN表达增加。HN在所有RRF和一些非RRF中均呈强阳性，其中大多数为1型纤维，通常比2型纤维需要更高的能量。HN在这些纤维中定位于线粒体。在对琥珀酸脱氢酶反应强烈的小动脉中，HN表达也增加。我们对肌肉TE671细胞的实验表明，合成HN通过直接作用于线粒体来增加细胞ATP水平的可能性。从这些在体内和体外的研究结果，我们建议，HN表达可能会被诱导在MELAS肌肉中受影响的纤维和血管内的能量危机，并进一步成为MELAS的一个可能的治疗候选人。
Humanin (HN) was originally identified as an endogenous peptide that protects neuronal cells from apoptosis induced by various types of Alzheimers disease-related insults. We have previously indicated that HN increases cellular ATP levels and speculated that this peptide may rescue energy-deficient cells in mitochondrial disorders. Here, we report, for the first time, increased HN expression in skeletal muscles from patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). HN was strongly positive in all ragged-red fibers (RRFs) and some non-RRFs, and most of them were type 1 fibers generally requiring higher energy than type 2 fibers. HN in these fibers was localized in mitochondria. HN expression was also increased in small arteries that strongly reacted for succinate dehydrogenase. Our experiments on muscular TE671 cells indicated the possibility that synthesized HN increases cellular ATP levels by directly acting on mitochondria. From these in vivo and in vitro findings, we propose that HN expression might be induced in response to the energy crisis within affected fibers and vessels in MELAS muscles and further be a possible therapeutic candidate for MELAS.