What is Caspase Activity?

Helga George

Caspase activity is due to a group of very complex enzymes that regulate programmed cell death, or apoptosis, in multicellular organisms. The enzymes involved in this activity are a subtype of a class of proteases—enzymes that degrade other proteins. There are several types of caspases that have different functions in causing apoptosis. Alterations in the regulation of apoptosis can lead to cancer or autoimmune disease, so there is much interest in better understanding the biochemistry and genetics of caspase activation in human cells using more simple organisms.

Apoptosis is often carried out with fruit flies.
Apoptosis is often carried out with fruit flies.

To keep the cells from self-destructing, caspases are kept in an inactive state. Such inactive enzymes are known as zymogens. Once the process of apoptotic death has been initiated, the caspases are activated by having part of their structure cleaved. Unlike many important cellular factors, these enzymes are kept in the cell already made, but in a latent state, ready to be activated as soon as they are needed.

Caspase activity is due to a group of very complex enzymes that regulate programmed cell death, or apoptosis.
Caspase activity is due to a group of very complex enzymes that regulate programmed cell death, or apoptosis.

There are two major classes of caspase activity that activate apoptosis. The first are initiator caspases, which are regulated by inhibitors. These enzymes are activated as soon as the process of programmed cell death is induced. The active initiator caspases cleave the inactive effector caspases, which then activate apoptosis.

One of the key processes of apoptosis is the breakdown of chromosomal DNA into its individual units. The effector caspases inhibit the enzymes that repair damaged DNA. They also break proteins, such as lamin, that keep the nucleus together as one unit. Additionally, effector caspase activity can cause the nuclear DNA to fragment.

With such dramatic changes happening, the cell dies, which is not necessarily bad for the organism. It is normal for a person to have tens of billions of cells a day die, and new ones form. The problem is when the regulation of apoptosis goes awry. With too little apoptosis taking place, cells in that tissue can spread and form a tumor. If there is too much apoptosis, atrophy can take place.

Definitive studies of the effects of enzymes rely on a number of factors, including the study of mutants that lack the activity. It is difficult and unethical to carry out such studies in humans. Frequently, work with apoptosis is carried out with nematodes or fruit flies.

To keep confusion to a minimum, caspases are numbered, starting with caspase 1 and going through 12. Given the complexity of this group of enzymes, it would not be surprising if more enzymes with this type of activity were discovered. Aside from their role in programmed cell death, these enzymes are also involved in inflammation, cell injury, and in development.

Caspases belong to a particular class of proteases, known as cysteine proteases. Proteases are classified either by the substrates they use or by the nature of their active site. Cysteine proteases are defined by the latter grouping and all have the amino acid cysteine in their active site.

There are a large number of commercial kits available for detecting caspase activity. They are based around measuring the protease activity as the zymogen is processed to an active enzyme. Caspase activity detection may also involve function, such as the initiation or execution of apoptosis.

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