Embryology Biology 441 Spring 2011 Albert Harris
Programmed Cell Death (of animal cells)
apoptosis (and other causes)
* Between fingers and toes. (duck-like webbed feet otherwise)
* Tadpole tail, gills, & many other tissues during metamorphosis
* 99% of b-lymphocytes: that make anti-self antibodies; also t-lymphocytes
* Virus-infected cells, when you are immune; t-lymphocytes induce cell death
* 131 specific cells in Caenorhabditis elegans (nematode) cell lineage.
?Cartilage cells being replaced by bone? (this hasn't yet been proved to me)?
Anchorage-dependent cells don't grow unless flattened/stretched onto something solid And many such cells will self-destruct unless spread out flat.
Much of the death of cancer cells in response to chemotherapy may really be caused by activation of self-destruction mechanisms, even though the drugs were designed to work by direct killing.
Cells whose DNA is damaged enough by UV light, or X-rays, or chemicals, halt at the G1-S cell cycle check-point (often called the "start" checkpoint) and wait there until their DNA has been repaired, & if their DNA isn't repaired, then the cells self-destruct.
Please understand that several different kinds of cell death occur, even several kinds of programmed death.
"necrosis" means NOT-programmed cell death, NOT self destruction; just cell death
Higher plants defend themselves from germs by programmed death of cells adjacent to infected cells.
Prof. Dangl of this department is a world expert on the mechanism of this cell death, which has turned out to be different from the animal cell mechanism, but is still tremendously important.
For many years, most scientists expected different programmed cell death mechanisms would be discovered, for mesonephros than for nematodes than for lymphocytes etc.
But evidence proves one major mechanism causing all these.
This self-destruct mechanism was re-named "apoptosis" in 1981. Before, the phenomenon had been called by other names. It had been discovered many, many years before, and always included in this course, which I had already been teaching then.
This new word was invented, based on the Greek word for the dropping of leaves in fall.
Much time has been wasted debating whether it should be pronounced APO-tosis, with the second P silent, analogous to pterodactyl.
Or A-Pop-tosis, with both Ps sounded, analogous to hymenoptera
A Scots Professor of Greek, who was a friend of a cell death researcher, was the person who proposed the word, & he said ancient Greeks wouldn't pronounce the second P. On the other hand, a student in this course who was originally from Greece and who spoke fluent Greek told me that modern Greeks would pronounce both Ps.
Since then, I pronounce both Ps, and about 3 times a year somebody "corrects" me. If this goes on, I will start not pronouncing the first P, and see what response that gets.
If you don't mind being corrected, I recommend pronouncing both Ps, so as to be understood. Or I may get a small campaign button, reading "Yes, thank you, I already know about not pronouncing the second P in apoptosis, but I am just stubborn."
I think thousands of scientists would be glad to buy such buttons.
Almost all body cells contain built-in self-digestion enzymes, always ready to destroy the cell from the inside out.
Body cells also have receptors and internal signaling methods for activating the enzymes.
Think of this as analogous to the explosives put on non-manned rockets launched from Cape Canaveral. If those rockets go off-course, radio messages set off the explosives.
The most important self-digestion enzymes are named "caspases." Some of these digest proteins; others are specific for other molecules.
Caspases are synthesized as pro-enzymes, analogous to trypsinogen in the pancreas.
That means part of the amino-acid chain blocks the active site. But if a proteolytic caspase molecule gets this blocking sequence removed, then a chain reaction occurs, with more and more caspases activated.
Bursting of inner mitochondrial membranes is the other main event, that contributes to apoptosis. Several reactive chemicals are released, and also the enzyme cytochrome oxidase.
If you watch cells self-destructing by apoptosis, it is easily recognized. Blebs of a special elongate shape protrude rapidly (bulges in the plasma membrane).
Some links to youtube videos of cells undergoing apoptosis:
Don't confuse these with the hemispherical blebs that cells form just before and after mitosis, and many other times.
There are also somewhat specific staining methods and molecular criteria, such as that DNA gets cleaved into pieces of certain sizes.
One of the proteins whose function is to control apoptosis is named bcl-2.
It inhibits apoptosis, and accumulates at or near the inner mitochondrial membrane.
Bcl-2 was discovered because too much of it causes the majority of cases a certain kind of cancer in humans, named follicular lymphoma.
A research group in New York studied chromosomes of lymphoma cells in hundreds of patients. They discovered many cases in which chromosome breakage and rejoining to a break in a different chromosome (a "translocation") had moved the promoter region of an antibody gene to an abnormal position next to the gene for some other protein.
Over-production of this other protein then occurred, often causing cancer.
They first discovered a gene they named bcl-1 (which isn't as important) A year or so later they discovered a new gene, which they named bcl-2.
Since then, they have also discovered bcl-3, which turned out to be a cyclin, and more recently bcl-4 through bcl-6.
But bcl-2 is the most important.
A gene almost identical to bcl-2 was separately discovered in C. elegans. (in which mutations in this gene causes abnormalities in programmed cell death). They call it a C.E.D gene.