Takeda A, Chiba S, Takaaki I, Tanamura A, Yamaguchi Y, Takeda N
Department of Internal Medicine, Aoto Hospital, Tokyo, Japan.
Jpn Circ J. 1998 Sep;62(9):695-9. doi: 10.1253/jcj.62.695.
Patients who have mitochondrial myopathy can present with specific pathological conditions (eg, diabetes mellitus and deafness). A 36-year-old woman presented with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). An investigation was conducted into whether the abnormalitiy of mitochondrial DNA (a T to C transition at position 3271 in the mitochondrial tRNA [Leu(UUR)] gene) influences nuclear DNA synthesis by cells in the heart, skeletal muscles, and brain. Myocardium, skeletal muscle, and brain tissues were stained with hematoxylin-eosin, and Masson trichrome for histopathology. Target nuclei taken from the myocardial and skeletal muscles and brain tissue were purified after removing debris by the modified Hedley method. These nuclei were stained with propidium iodide (PI) for analysis by flow cytometry. The number of nuclei in the G2M phase was bigger in myocytes of MELAS than in normal myocytes (Control) (MELAS myocyte: Control myocyte=24.9+/-7.3: 6.1+/-1.6%, p<0.005), but there was no significant increase in the G2M phase in brain tissue. The G1 phase was far more reduced in MELAS myocytes and skeletal muscle than in Controls (MELAS myocyte: Control myocyte=65.8+/-9.1: 88.0+/-3.2%, p<0.005; MELAS skeletal muscle: Control skeletal muscle=85.1+/-2.2: 90.1+/-3.2%, p<0.05), while there was no significant decrease of nuclei in the G1 phase in brain tissue. Increased amount of nuclei in the G2M phase in cardiac myocytes and skeletal muscle cells compared with that in neurons might depend on the capacity for proliferation and differentiation of these cells as compared with brain tissue. It was concluded that the mitochondrial DNA mutation (3271T-to-C) of MELAS may influence the nuclear DNA synthesis of cells in various tissues depending on their level of mitotic activity.
患有线粒体肌病的患者可能会出现特定的病理状况（如糖尿病和耳聋）。一名36岁女性患有线粒体肌病、脑病、乳酸性酸中毒和卒中样发作（MELAS）。研究了线粒体DNA的异常（线粒体tRNA[Leu(UUR)]基因第3271位由T向C的转变）是否会影响心脏、骨骼肌和脑组织中细胞的核DNA合成。心肌、骨骼肌和脑组织用苏木精-伊红染色，并进行Masson三色染色以进行组织病理学检查。采用改良的Hedley方法去除碎片后，从心肌、骨骼肌和脑组织中纯化目标细胞核。这些细胞核用碘化丙啶（PI）染色，通过流式细胞术进行分析。MELAS患者心肌细胞中G2M期的细胞核数量比正常心肌细胞（对照组）多（MELAS心肌细胞：对照组心肌细胞=24.9±7.3：6.1±1.6%，p<0.005），但脑组织中G2M期没有显著增加。MELAS患者的心肌细胞和骨骼肌中G1期比对照组减少得多（MELAS心肌细胞：对照组心肌细胞=65.8±9.1：88.0±3.2%，p<0.005；MELAS骨骼肌：对照组骨骼肌=85.1±2.2：90.1±3.2%，p<0.05），而脑组织中G1期的细胞核没有显著减少。与神经元相比，心肌细胞和骨骼肌细胞中G2M期细胞核数量增加可能取决于这些细胞与脑组织相比的增殖和分化能力。得出的结论是，MELAS的线粒体DNA突变（3271T向C）可能会根据细胞的有丝分裂活性水平影响各种组织中细胞的核DNA合成。
