Cell cycle of myocytes of cardiac and skeletal muscle in mitochondrial myopathy.
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.
Takeda
A
A
Department of Internal Medicine, Aoto Hospital, Tokyo, Japan.
Chiba
S
S
Takaaki
I
I
Tanamura
A
A
Yamaguchi
Y
Y
Takeda
N
N
D000328:Adult; D002453:Cell Cycle; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017241:MELAS Syndrome / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008931:Mitochondria, Muscle / Q000473:pathology; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D017354:Point Mutation; D013203:Staphylococcal Infections / Q000150:complications
D004272:DNA, Mitochondrial