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Most apoptotic cells in mdx diaphragm muscle contain accumulated lipofuscin
Y Nakae1, P J Stoward, M Shono
1Department of Oral Anatomy 1, Tokushima University School of Dentistry, 3 Kuramoto-cho, Tokushima 770-8504, Japan. Yoshiko.Nakae@ma3.seikyou.ne.jp
Abstract:
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.
Insights
Lipofuscin (LF) accumulates in dystrophic mouse muscles, indicating increased oxidative stress. This pigment is linked to apoptosis in muscle cells, potentially impairing regeneration in muscular dystrophy.
Area of Science:
- Cellular Biology
- Muscle Physiology
- Oxidative Stress Research
Background:
- Lipofuscin (LF) is an age-related pigment accumulating in long-lived cells due to oxidative damage.
- Muscular dystrophy (MD) involves muscle degeneration and regeneration cycles.
- Oxidative stress is implicated in various cellular dysfunctions.
Purpose of the Study:
- To investigate lipofuscin accumulation in the diaphragm muscles of dystrophic (mdx) mice.
- To determine the relationship between lipofuscin and apoptosis in mdx muscle cells.
- To explore the impact of oxidative stress on muscle regeneration in mdx mice.
Main Methods:
- Comparison of diaphragm muscle from 10-week-old mdx mice and age-matched C57BL/10 control mice.
- Histological analysis to detect lipofuscin accumulation in myofibres, myosatellite cells, and interstitial cells.
- Assessment of apoptosis in mdx diaphragm muscle and correlation with lipofuscin presence.
Main Results:
- Significant lipofuscin accumulation was observed in mdx mouse diaphragm muscles, but not in controls.
- mdx muscles showed higher susceptibility to oxidative stress compared to normal muscles.
- 74-79% of apoptotic cells in mdx diaphragm contained lipofuscin, versus 12-20% of non-apoptotic cells.
Conclusions:
- Lipofuscin accumulation is a marker of oxidative stress in dystrophic mdx muscles.
- Apoptosis of muscle cells, particularly myosatellite cells, is associated with lipofuscin.
- Impaired muscle regeneration in mdx mice may result from lipofuscin-linked apoptosis due to oxidative injury.
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