Apoptosis is suspended in muscle of mitochondrial encephalomyopathies

被引:35
作者
Ikezoe, K
Nakagawa, M
Yan, CZ
Kira, J
Goto, Y [1 ]
Nonaka, I
机构
[1] NCNP, Natl Inst Neurosci, Dept Mental Retardat & Birth Defect Res, Kodaira, Tokyo 1878502, Japan
[2] NCNP, Dept Ultrastruct Res, Natl Inst Neurosci, Kodaira, Tokyo 1878502, Japan
[3] Kyushu Kosei Nenkin Hosp, Dept Neurobiol, Kitakyushu, Fukuoka 8068501, Japan
[4] Kyushu Univ, Dept Neurol, Neurol Inst, Grad Sch Med Sci, Fukuoka 8128502, Japan
[5] Univ Tokyo, Dept Plast Surg, Grad Sch Med Sci, Tokyo 1138655, Japan
关键词
apoptosis; mitochondria; X-linked inhibitor of apoptosis protein; ragged-red fiber; mitochondrial encephalomyopathy;
D O I
10.1007/s00401-001-0502-8
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Over the past few years, many studies have been done on the apoptotic involvement in muscle fiber degeneration in various myopathies, but the occurrence of apoptosis in muscles of mitochondrial encephalomyopathies is still controversial. To confirm whether apoptotic processes are truly related to muscle fiber degeneration in mitochondrial encephalomyopathies, we performed the TUNEL method not only at the light microscopic (LM) but also at the electron microscopic (EM) level for muscles of five MELAS, five CPEO and five MERRF patients and five control muscles. Immunohistochemical studies of Bcl-2, Bax, cytochrome c, Apaf-1, activated caspase-3 and human inhibitor of apoptosis protein XIAP, and immunoblotting of Apaf-1 and XIAP were also carried out. In LM-TUNEL, MELAS, CPEO and MERRF patients had only very small numbers of TUNEL-positive myonuclei: 0.13+/-0.10%, 0.15+/-0.14% and 0.04+/-0.09%, respectively. Almost all of them were seen in ragged-red fibers (RRFs). EM-TUNEL showed no significant increase of DNA fragmentation in RRFs despite mild peripheral chromatin condensation. However. Bax and Apaf-1 expression and cytochrome c release from mitochondria were seen in RRFs. Caspase-3 activation was confirmed in 9.0+/-3.7%, 12.0+/-4.4% and 12.4+/-3.8% of RRFs in MELAS, CPEO and MERRF, respectively, but not in control muscles. Almost all RRFs showed sarcoplasmic expression of XIAP. Thus, there is a possibility that, although apoptotic reactions started in muscles of mitochondrial encephalomyopathies, their execution is rarely completed. Sarcoplasmic expression of XIAP probably leads to the suspension of the apoptotic process in mitochondrial encephalomyopathies.
引用
收藏
页码:531 / 540
页数:10
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