Most apoptotic cells in mdx diaphragm muscle contain accumulated lipofuscin.
An age-related pigment, lipofuscin (LF), which accumulates in postmitotic, long-lived cells, is formed by the oxidative degradation of cellular macromolecules by oxygen-derived free radicals. In the present study we show that LF is accumulated in some myofibres, myosatellite cells and interstitial cells in the diaphragm muscles of the X chromosome-linked muscular dystrophic (mdx) mice at the age of 10 weeks when repetitive cycles of de- and regeneration of myofibres occur. In contrast, LF is virtually absent in diaphragm muscles of age-matched C57BL/10 (C57) normal control mice. Therefore, mdx muscle is more susceptible to oxidative stress than normal muscle. We hypothesise that gene-regulated cell death (apoptosis) occurs in dystrophic muscle cells that accumulate LF as a consequence of either oxidative stress or injury. We found that 74-79% of apoptotic myosatellite cells, interstitial cells and myofibres in mdx diaphragm contain accumulated or dotted LF granules, but only 12-20% of non-apoptotic cells contain LF. Apoptotic cells are very rare in the diaphragm of age-matched C57 control mice. This suggests that the regeneration of mdx diaphragm muscle initiated from myosatellite cells is impaired by their apoptosis as the result of either oxidative stress or a product of oxidative injury.
Nakae
Y
Y
Department of Oral Anatomy 1, Tokushima University School of Dentistry, 3 Kuramoto-cho, Tokushima 770-8504, Japan. Yoshiko.Nakae@ma3.seikyou.ne.jp
Stoward
P J
PJ
Shono
M
M
Matsuzaki
T
T
D000818:Animals; D017209:Apoptosis; D003964:Diaphragm / Q000166:cytology / Q000378:metabolism*; D005453:Fluorescence; D020287:In Situ Nick-End Labeling; D008062:Lipofuscin / Q000378:metabolism*; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018613:Microscopy, Confocal; D018384:Oxidative Stress
D008062:Lipofuscin