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What triggers programmed cell death in humans? Is it decided by the brain (for the entire body)? Or is it a local decision of a cell by its environment? Something else?

I realize that there might be different cases. But I'd like to get a general idea of where (and why, actually) does this happen.

EDIT

As linked to by a comment below - one type of cell-death (Necrosis) just "happens" to a cell. And perhaps there are other types that are decided by the cell. What I'm asking about (and trying to understand more) is about the idea that cell-death might be initiated externally to the cell because it would be beneficial to the whole organism. Such as "the separation of fingers and toes" mentioned in Wikipedia . "Who" would initiate it? Are there examples of the CNS initiating it? Notifying the cell by nerves? By hormones? Are they initiated by neighboring cells? (And if so - what cells have the "clout" to send such signals?)

What I'm trying to understand is who decides when a cell dies in those cases where it's not the cell itself.

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  • $\begingroup$ Have you read the wikipedia article on apoptosis? If not, please read it, then edit your question to narrow it down to a specific question about the process. As it stands now, this question is far too broad, as there are many different ways of triggering apoptosis, and many different pathways within the cell for effecting it. $\endgroup$ – MattDMo Jan 1 '15 at 22:59
  • $\begingroup$ @user133943 you should edit your question to specify that you mean regulated cell death (as it applies to development). As it is written, your question is too broad $\endgroup$ – Luigi Jan 2 '15 at 3:27
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The answer is, in part, it depends. Let's think of the PI3K/AKT pathway. Akt actively phosphorylates BAD which abrogates the Bax/Bak apoptosis pathway. RTK's at the plasma membrane activate this pathway when bound with survival factors. In the absence of survival factors, Akt would become dephosphorylated and you'd have a net movement toward apoptosis. In a particular form of cell death called anoikis, this could be as simple as detaching from the extracellular matrix. So anything that halts the binding of survival factors could play a role.

In the case of immune response, activated Tc cells can induce apoptosis by secreting pore-forming enzymes as well as enzymes that directly activate caspases. The Tc cells also express Fas on their membrance which is involved in the extrinsic apoptosis pathway. TNF (tumor necrosis factor) may also bind cell surface receptors as sort of a death factor, and push towards apoptosis.

These are just examples, some generic searches about apoptosis, necroptosis, entosis, and a myriad of other programmed death mechanisms will yield a very comprehensive overview.

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  • $\begingroup$ Thank you. If I understand you correctly - the first type you mentioned is (very generally) - an example of cells having a built in mechanism to detect a condition (such as being detached from their natural surroundings) that warrants cell death. The second - more pertaining to my question - would be: the immune system. (Please feel free to correct me if I'm wrong.) $\endgroup$ – 123 Jan 20 '15 at 20:09
  • $\begingroup$ @user It's a very textbook answer, here's a review of some apoptotic regulation mediated by extracellular signaling. It's a complex response that may be regulated by paracrine, autocrine, neuronal signals in addition to cell-cell interaction. There's a bunch of different pathways that all differ in their mechanism of action. $\endgroup$ – CKM Jan 20 '15 at 20:31
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One event that comes to mind is the use of radiation on cancer patients. Radiation is an external event that can trigger apoptosis in humans 1. When cancer patients receive radiation, the treatment is localized. The brain isn't telling the cells to die it is the radiation effects on the cell.

Ionizing radiation can also induce apoptosis via the generation of free radical oxygen species 2.

Free radical oxygen species does this by searching for an electrons in the molecular make up of the cell 3.

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