Every day, in organs such as the liver or bone marrow, our bodies produce billions of new cells. Why, then, do we not resemble rapidly inflating balloons, rather than people? Because, normally, this growth is exactly matched by cell death, through a deliberate and controlled process: apoptosis – programmed cell death.
Apoptosis does more than maintain a balance though, it prevents old or damaged cells from going off the rails, it stops infections from running amuck, and gets rid of cells which are simply no longer needed. Under normal circumstances apoptosis is exquisitely controlled – well illustrated by the forming of delicate fingers from a paddle-like hand during development – but this control can go wrong, or be circumvented. When that happens, there are problems. A cancer cell becomes deaf to the suicide demands of its neighbours, self-reactive T and B-cells slip through the net and cause autoimmune disease, viruses somehow prevent or delay apoptosis, worsening the infection. There is a long list of ills in which some failing of apoptosis has been implicated.
By puzzling out the environmental and internal cellular mechanisms of apoptosis – where and how the program has been broken – we have a much better chance of combating these ills, understanding how they arise, and how they can be detected, treated, or even prevented.
In vitro and In vivo apoptosis assay kits, including:
30% Discount on the NEW MitoPT™ Kits - assess changes in mitochondrial membrane potential and detect mitochondrial depolarization
IMGENEX introduces pSIVA, the first reversible apoptosis probe for detecting phosphatidylserine (PS) exposure on plasma membranes. Exclusively available from IMGENEX.
pSIVA (Annexin XII) is an Annexin based, polarity sensitive probe for the spatiotemporal or kinetic analysis of apoptosis and other forms of cell death. pSIVA (Annexin XII) binding is reversible enabling researchers, for the first time, to detect transient PS exposure which is associated with normal physiological processes as well as with reversible or rescuable apoptosis cell death events.
pSIVA (Annexin XII) is conjugated to IANBD, a polarity sensitive dye that fluoresces only when pSIVA is bound to the cell membrane. pSIVA’s membrane-bound dependent fluorescence and reversible binding properties are a technological leap for detecting PS exposure and offer additional information on the apoptosis pathway and cell survival compared to Annexin V conjugates. Annexin V binding is nonreversible.
pSIVA Product Citations
1. Engineering a polarity–sensitive biosensor for time-lapse imaging of apoptotic processes and degeneration. Kim YE, J Chen, JR Chan, R Langen. Nat Methods 7:67-73 (2010).
2. Monitoring apoptosis and neuronal degeneration by real-time detection of phosphatidylserine externalization using a polarity-sensitive indicator of viability of apoptosis. Kim YE, J Chen, R Langen, JR Chan. Nature Protocols 5:1396-1405 (2010).
3. A compact ß model of huntingtin toxicity. Zhang CQ, Yeh T-l, A Leyva, LG Frank, J Miller, YE Kim, R Langen, S Finkbeiner, ML Amzel, CA Ross, MA Poirier. JBC 286:8188-8196 (2011).
There's a large number of pathways and a huge number of different protein-protein interactions involved in apoptosis. As a brief example, one of the most well studied families of apoptosis regulating proteins, found in all of our bodies cells, is that of the Bcl-2 family.
Under normal circumstances there's a complicated and precise balance between the pro-apoptotic and anti-apoptotic proteins, binding to one another and regulating each others functions. Normally the potently anti-apoptotic protein Bcl-xL keeps it's equally potent pro-apoptotic partner, Bak, in check, binding and deactivating it. Normally the balance between Bcl-xL and Bak is well controlled, only shifting when a cell goes awry somehow, causing apoptosis to prevent any further damage. However, mutations can result in the anti-apoptotic Bcl-xL being over expressed, preventing apoptosis, despite increasing levels of Bak. This can result in uncontrolled cell division - cancer.
The video below briefly introduces the intrinsic (of which Bcl-xL is a member) and extrinsic pathways of apoptosis and why they are important in cancer research. The video was produced by Genentech BioOncology.