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Apoptosis

Apoptosis [from a Greek word meaning “falling off”] is simply defined as “programmed cell death” in which cells that are no longer needed, perish, by activating an intracellular cell death program. Apoptosis is a natural phenomenon and each day, billions of cells in the human body are known to die through this process.

All cells in a human body originate from the fertilized egg. During embryonic and fetal periods, the number of cells increases exponentially. They mature and specialize to form various tissues and organs of the body. In parallel to this generation, cells also start dying to maintain an appropriate, healthy number in the tissues. While it seems like a waste of cellular machinery to produce all these cells only to kill them ultimately, apoptosis is a very critical function that maintains a delicate balance, which when skewed, could lead to disastrous results, potentially even jeopardizing the survival of an organism. Excessive apoptosis results in atrophy whereas insufficient apoptosis causes uncontrolled cell proliferation resulting in cancers.

The Discovery of Apoptosis

The mystery of Apoptosis has baffled scientists for years. Three scientists that dedicated their lives to this field of research include Sydney Brenner, Robert Horvitz and John Sulston. All three worked in different labs but the one thing common to all of them was the model organism that they worked with - the non-parasitic, transparent nematode – Caenorhabditis elegans (C.elegans).

The fertilized egg undergoes a series of cell divisions leading to differentiation and specialization. In C. elegans, all cell divisions and differentiations were identical between individual to individual. This feature made it possible to construct a lineage for all cell divisions. Through such mapping, the scientists found that 1090 cells were generated during development out of which precisely 131 cells were eliminated by the process of cell death, resulting in an adult nematode with 959 somatic cells. Through their combined efforts, these scientists demonstrated the genetic regulation of organ development and cell death.

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Nobelprize.org

Copyright© The Nobel Foundation

Sydney Brenner demonstrated that specific gene mutations could be induced in the C.elegans genome by treatment with a compound called Ethyl Methane Sulphonate (EMS), and that different mutations could be linked to specific genes and specific effects on organ development.

Read the classic – The Genetics of Caenorhabditis elegans

 

Image courtesy:
Nobelprize.org

Copyright© The Nobel Foundation

Robert Horvitz discovered and characterized some of the key genes involved in the cell death process in C.elegans(ced-3, ced-4 and ced-9) and demonstrated their interaction with one another while showing that corresponding genes existed in human beings as well

Read the classic – Genetic control of programmed cell death in the nematode C. elegans

 

Image courtesy:
Nobelprize.org

Copyright© The Nobel Foundation

John Sulston showed that specific cells undergo programmed cell death as part of the normal differentiation process. He identified the first mutation in a gene that participated in cell death.

Read the classic - Post-embryonic cell lineages of the nematode, Caenorhabditis elegans

What causes Apoptosis?

Scientists in recent years have unraveled the molecular mechanisms and pathways underlying this phenomenon. Apoptosis is known to be mediated by an intracellular proteolytic cascade, orchestrated by proteolytic enzymes called caspases. In the best studied pathway, it was found that apoptotic proteins in mitochondria, belonging to the Bcl-2 family, are induced thereby causing a mitochondria to release its contents, ultimately leading to the events of a caspase cascade. In contrast to necrosis, which is an explosive and damaging inflammatory response, apoptosis is a some what implosive process whereby a cell shrinks and condenses, its cytoskeleton collapses, and the nuclear envelope disassembles thereby subjecting chromosomal DNA to fragmentation. The altered cell surface causes a dying cell to be phagocytosed [eaten away] rapidly by a specialized, scavenging cell called the macrophage.

Despite the numerous advancements in the field of apoptosis research, GenScript realizes that a lot more still needs to be done and it is committed to providing high quality products and services that will accelerate future discoveries. Studies of proteins involved in other critical pathways are made easier by our products and gene, peptide, protein, antibody, cell line and apoptosis assay services as part of our discovery services.

Recent Publications on Apoptosis that cite GenScript

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