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[Apoptosis and myopathies]
Abstract:
Recently a new type of cell death, apoptosis, was reported in the biological and many other fields. In an attempt to determine whether the Fas-Fas-ligand mediated apoptosis operates in the pathologic process of human myopathies, we examined the expression of Fas antigen, the synthesis of Fas-ligand mRNA, and the presence of chromosomal DNA fragmentation in the muscles from patients with various human muscle disorders. The Fas antigen of a whole molecule that can transduces the apoptotic signal into the cytoplasm was expressed on the muscle fibers of patients with various muscle wasting diseases. Its expression on muscle fibers was not disease specific, and the frequency of it becomes high according to the extent of the alteration of the muscle pathology. However, there was no evidence of operating the apoptotic process, that is no DNA fragmentation by TUNEL method. Furthermore, no Fas-ligand synthesis was detected in the diseased muscle tissue by RT-PCR method. Our data suggest that the expression of Fas antigen on muscle fibers in diseased muscles might be related to unknown biological functions other than "apoptosis" in the process of muscle fiber injury.
Insights
Fas antigen is present in muscle fibers of patients with muscle wasting diseases, but it does not trigger apoptosis. This suggests Fas has other roles in muscle fiber injury beyond programmed cell death.
Area of Science:
- Cell Biology
- Neurology
- Immunology
Background:
- Apoptosis, a form of programmed cell death, is a significant biological process.
- The Fas-Fas-ligand system is a known mediator of apoptosis.
- Its role in human myopathies, particularly muscle wasting diseases, remains unclear.
Purpose of the Study:
- To investigate the involvement of the Fas-Fas-ligand pathway in the pathology of human myopathies.
- To determine if Fas-mediated apoptosis occurs in diseased human muscle fibers.
Main Methods:
- Examined Fas antigen expression on muscle fibers using immunohistochemistry.
- Assessed Fas-ligand mRNA synthesis via reverse transcription-polymerase chain reaction (RT-PCR).
- Detected chromosomal DNA fragmentation using the TUNEL assay to identify apoptosis.
Main Results:
- Fas antigen was expressed on muscle fibers in various muscle wasting diseases, with expression levels correlating with pathological alterations.
- No evidence of DNA fragmentation (apoptosis) was found in diseased muscle tissues using the TUNEL method.
- Fas-ligand synthesis was not detected in the diseased muscle tissue samples.
Conclusions:
- The presence of Fas antigen on muscle fibers in myopathies does not necessarily indicate Fas-mediated apoptosis.
- The observed Fas antigen expression may be linked to other, yet unidentified, biological functions in muscle fiber injury.
- The Fas-Fas-ligand apoptotic pathway is unlikely to be a primary mechanism in the studied human myopathies.