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Single muscle fiber analysis of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS)
Author(s) -
Tokunaga Makoto,
Mita Shuji,
Murakami Tatsufumi,
Kumamoto Toshihide,
Uchino Makoto,
aka Ikuya,
Ando Masayuki
Publication year - 1994
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410350407
Subject(s) - mitochondrial myopathy , lactic acidosis , melas syndrome , cytochrome c oxidase , biology , mitochondrial dna , mitochondrial encephalomyopathies , encephalopathy , mitochondrial encephalomyopathy , mitochondrion , myopathy , microbiology and biotechnology , medicine , endocrinology , biochemistry , genetics , gene
We examined muscle sections from 3 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS), using single‐fiber polymerase chain reaction, histochemistry, and in situ hybridization. Most type 1 ragged‐red fibers showed positive cytochrome c oxidase activity at the subsarcolemmal region, while type 2 ragged‐red fibers had little cytochrome c oxidase activity. However, there was no difference in the amount of total (mutant and wild‐type) mitochondrial DNAs (mtDNAs) and the proportion of mutant mtDNA between type 1 and type 2 ragged‐red fibers. These observations suggest that mitochondrial proliferation and nuclear factors affect muscle pathology, including cytochrome c oxidase activity, in MELAS. Total mtDNAs were greatly increased in ragged‐red fibers (about 5–17 times over those in non–ragged‐red fibers). The proportion of mutant mtDNA was significantly higher in ragged‐red fibers (88.1 ± 5.5%) than in non–ragged‐red fibers (63.2 ± 21.6%). Thus, the amount of wild‐type mtDNA as well as mutant mtDNA was increased in ragged‐red fibers in MELAS, failing to support the contention of a replicative advantage of mutant mtDNA. The proportion of mutant mtDNA was significantly higher in the strongly succinate dehydrogenase–reactive blood vessels (83.2 + 4.2%) than in non–succinate dehydrogenase–reactive blood vessels (38.8 ± 16.2%). It seems likely that systemic vascular abnormalities involving cerebral vessels lead to the evolution of stroke‐like episodes in MELAS.