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What Is Caspase Activation?

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  • Written By: H. Colledge
  • Edited By: Heather Bailey
  • Last Modified Date: 23 November 2016
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Caspases are enzymes which break down human cells into small fragments as part of what is called apoptosis, or programmed cell death. During this process, caspases cleanly dismantle cells that are not required or that could cause problems if left intact. To prevent caspases from breaking down cells all the time, they normally exist in an inactive form. Caspase activation is triggered by substances binding to cells and signals from mitochondria in the cell, or the arrival of immune cells, set off a series of events. The caspases activate each other in turn, ending with those which are able to break down the cell into small pieces for use by its neighbors.

Apoptosis is different from the process that happens when cells are damaged and inflammation occurs. Due to the action of caspases, cells are neatly taken apart, without any of the swelling or other disruptive changes associated with inflammation. This is important in the developing embryo, where unwanted cells are continually removed. Caspase activation and apoptosis are also useful when cells are infected by viruses, as the cells can be eliminated before the virus spreads. Another benefit of caspase activation and apoptosis is that cells with mutations can be taken out of service efficiently, preventing cancers from developing.

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Different caspase activation pathways exist, one of which involves substances binding to special receptors, known as death receptors, on the cell surface. Once this binding has occurred, the death receptors group together. Parts of the receptors protrude inside the cell and, when these cluster together, certain proteins are attracted. These proteins from inside the cell bind to the death receptors and trigger the caspase activation sequence.

Sometimes immune cells called lymphocytes cause caspase activation. They bind to the death receptors on the cell surface, presenting them with a special enzyme or with parts of damaged cells or viruses. Caspase activation can also occur when stress affects the cell. This stress could result from a viral infection, the effects of radiation or chemicals, or a lack or excess of certain substances. The stress causes tiny structures known as mitochondria, which produce energy inside the cell, to release a protein which activates the caspase sequence.

When caspase activation has taken place, a series or cascade of reactions occurs, similar to that seen in the complement system. Caspases become activated and activate other caspases in turn, until the effector caspases, such as caspase 6 and caspase 3, become active. These effector caspases break down important cell structural proteins. Caspases enable fragmentation of the cell's DNA by activating enzymes that can break it down. At the same time as DNA is dismantled, caspases inhibit the enzymes responsible for repairing it.

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