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Programmed cell death: concept, mechanism and control
1Centre for Advanced Study in Cell and Chromosome Research, University of Calcutta, India.
Biological Reviews of the Cambridge Philosophical Society
|August 1, 1992
Summary
Programmed cell death, or apoptosis, is a genetically controlled process crucial for physiological functions. Understanding the molecular mechanisms and genetic regulation of apoptosis is key to its study.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Programmed cell death (apoptosis) is a physiological process involving active cellular participation.
- Apoptosis is genetically controlled and can be induced by various stimuli, but its precise mechanisms and intensity-dependent roles require further investigation.
- Morphological and biochemical changes characterize apoptotic cells, including chromatin fragmentation and plasma membrane alterations facilitating phagocytosis.
Purpose of the Study:
- To elucidate the underlying mechanisms of apoptosis and its regulation.
- To investigate whether all cells can undergo apoptosis or if it is tissue-specific.
- To explore the role of macromolecular synthesis and specific genes in the apoptotic cascade.
Main Methods:
- Morphological observation of apoptotic cells.
- Biochemical analysis of DNA fragmentation and enzyme activity (Ca2+, Mg2+-sensitive neutral endonuclease).
- Investigation of RNA and protein synthesis requirements for apoptosis.
- Molecular studies identifying specific genes and their products involved in apoptosis (e.g., ced gene, TRPM-2/SGP-2, c-fos, c-myc).
Main Results:
- Apoptosis involves DNA cleavage by a Ca2+, Mg2+-sensitive endonuclease, inhibited by zinc, with calcium playing a key role in enzyme activation.
- Most apoptotic cells require RNA and protein synthesis; inhibition of macromolecular synthesis delays or prevents apoptosis.
- Specific genes and their products, such as TRPM-2/SGP-2, c-fos, and c-myc, are sequentially induced during apoptosis.
- Certain genes must remain transcriptionally active and demethylated for programmed cell death.
Conclusions:
- Apoptosis is a complex, genetically regulated process involving specific biochemical and molecular events.
- Calcium signaling and macromolecular synthesis are critical for initiating and executing apoptosis.
- Further experimental studies are needed to compare apoptosis induction across different cell types and fully elucidate its genetic control.