Re.: APOPTOSIS - Programmed cell death (Information needed)

Kurt Schaudt olxsc01 at mailserv.zdv.uni-tuebingen.de
Mon Mar 14 15:13:14 EST 1994

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>From: md93mgk at brunel.ac.uk (Michael G Karras)
>Subject: APOPTOSIS - Programmed cell death (Information needed)
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>Date: Mon, 14 Mar 1994 10:50:16 GMT
>I'm coming back seeking information on apoptosis aka programmed cell death
>After seeing this documentary on BBC television I had this very specific
>query. It was said that cell death comes after stop of communication
>between similar cells. It was also said that CED-9 gene is responsible
>for this death. I'm not anexpert on the subject I'm an electronics
>engineer that has just basic knowledge on life and bio subjects. 
>My query was if that is true how it comes and the egg cell does not need
>this communication when it's separated by the others. Is there any 
>when we talk about egg cells and other cells when apoptosis is concerned?
>Please I need an answer. It has been troubling me for over than a month
>and I would like to know more about it. I read a few technical documents
>but I could not understand anything because it was "too" technical.
>I would appreciate if anybody could forward this message to anybody who 
>could give me an answer. I am desperate about it.
>Thank you very much in advance
>Michael Karras

Dear Michael,

Consider that apoptosis is mediated by signalling events within the cell.
 Cell surface receptors (peptides or proteins fixed on the cell membran,
capable of binding other peptides), like the APO1 - receptor (capable 
of mediating apoptosis), interact with most specific suitable other 
substances (eg. peptides), resulting in a particular intracellular signal.
 This signal may induce apoptosis (eg. by enhancing calcium influx and
so activating the endonucleases) or may prevent the cell from it (eg. by 
downregulating apoptotic signals), depending on the kind of the receptor.
 Expression of these receptors depends on the genetic program the cell is
processing - this program depends on the kind of differentiation of the 
cell and on its state of differentiation.
 Apoptosis anyway is a process of strongly making sense. If a cell 
differenciated to be a member of a particular tissue with a special 
function escapes to another tissue, it is not desirable that this cell 
will overcome and even divide. 
 So this cell will express a special kind of receptor (called adhesion 
molecule) which will bind to another receptor molecule (same type) of a 
cell of the same type and both of this receptors will hinder the other 
to produce an apoptotic signal. 
 Within the particular tissue most of these adhesion molecules are bound 
to a suitable other of the neighbourhood cell and so apoptosis is 
prevented. If such a cell escapes from the tissue and looses contact to 
the appropriate cells, the now "free" receptor molecules will mediate an 
apoptotic signal event (or they will stop antiapoptotic signal events).
 The special kind of such receptors (adhesion molecules) depend strongly on 
the differentiation status of the cell. So eg. liver cells only will 
express receptors specific for liver cells, if they escape eg. to the 
stomach, they will lack their appropriate partner molecules and so 
undergo apoptosis.
 Another example for apoptosis is the immune system. Its apoptotic events 
are special cases of the "common apoptosis". For they lack tissue like 
cell - cell contact their "communication" is mediated by so called 
"interleukines" (water soluble peptides in the blood and the tissue 
fluids). Here apoptosis is necessary because at the beginning of an 
infection suitable cells are expanded in greatest extend (by deviding) to 
overcome the infection quickly, at the end of the infection however these 
(exponential !) cellular growth events must be extinguished very quickly and 
carefully to prevent uncontrolled growth of cells (as seen in leucaemic 
 Growth of this kind of cells is mediated by these interleukins which's 
signalling events prevent the cell from apoptosis.

Note: these cells of the immune system dont need direct cell - cell 
contact for not to undergo apoptosis. The reason for this is the lack of 
molecules on the cell surface which need direct cell - cell contact for 
preventing apoptosis (but they are replaced in function by the 
interleukin receptors). That doesn't say that immune cells have no 
adhesion molecules at all but in immune cells they have different 
functions (due to other molecules on the cell's surface).

This is underlining the fact that the cell has greatest flexibility to 
alter its nature by expression particular molecules (on the cell surface) 
or not, governed by its special state of differentiaton.   

This remarks should help you to explain your question:
If the differentiation state of an egg cell is a genetic program which 
doesn't at all express receptors capable for mediating apoptosis it 
cannot undergo apoptosis.
You haven't  mentioned which kind of egg cells you meaned especially, but 
this is true for all kinds: 
if you meaned for example fish eggs, they after spawning lack cell - cell 
contact and so their genetic program after maturing will not express 
apoptotic mediating receptor molecules at all.
if you meaned eg. human eggs they of course will express receptor 
molecules specific for the tissues they are surrounded with in the normal 
case which prevents them from dividing in abnormal surroundings.

But note: apoptosis is not governed alone by those apoptotic signal 
events but also by expression of other gene products: the endonucleases 
themselfes (which mediates apoptosis by cleaving the cellular DNA into 
small and useless fractions), suppressors of these endonucleases, 
suppressors of their action on the DNA and so on ...

Hope this helps a little !

(And, as a natural scientist, I hope that answering this one question will 
arise a couple of new others - as usual in this kind of science.

By the way, I appreciate interest of non specialists in these things 
because their (at first sight simple to answer) questions in praxi proove 
to be answered not quite so simple than expected and, maybe, they may be 
able to give worthy contributions from their fields and their points of 
Especially specialists in electronics may recognize phenomena in control, 
regulation and biological "control engineering" earlier than "only" 
specialists in biology do, so I want to encourage all people (even non 
biologists) with interest in those phenomena to enter such discussions.) 

Kurt Schaudt, kschaudt at mailserv.zdv.uni-tuebingen.de

Medical School of Tuebingen

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