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Stress-induced apoptosis and the sphingomyelin pathway
L A Peña1, Z Fuks, R Kolesnick
1Laboratory of Signal Transduction, Memorial Sioan-Kettering Cancer Center, New York, NY 19921, USA.
Biochemical Pharmacology
|March 7, 1997
Summary
The sphingomyelin pathway, crucial for cell signaling, generates ceramide to control cell fate. This review details how acid sphingomyelinase (ASMase) activation by stress or receptors triggers apoptosis.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Signaling
Background:
- The sphingomyelin pathway is a conserved signaling system generating the second messenger ceramide.
- Sphingomyelin degradation is mediated by acid and neutral sphingomyelinase (SMase) isoforms.
- This pathway is activated by diverse receptors and environmental stresses in mammalian cells.
Purpose of the Study:
- To review the mechanisms of acid sphingomyelinase (ASMase) activation.
- To explore ceramide signaling in the apoptotic response.
- To differentiate roles of ASMase and neutral SMase in cellular signaling.
Main Methods:
- Review of existing literature on sphingomyelinase activation and ceramide signaling.
- Analysis of signaling cascades linked to ASMase and neutral SMase.
- Examination of stress and receptor-mediated activation pathways.
Main Results:
- Acid SMase activation is linked to the SAPK/JNK cascade and apoptosis.
- Neutral SMase activation is associated with the ERK cascade and inflammation.
- Environmental stresses activate ASMase directly, while cytokine receptors signal via death domains.
Conclusions:
- Ceramide's role in cell fate is context-dependent, mediating proliferation or apoptosis.
- ASMase activation is a key mechanism initiating stress-induced apoptosis.
- Understanding ASMase activation pathways is critical for deciphering cellular responses to stress and disease.