THE ROLE OF CASPASE-3 IN APOPTOSIS
The term apoptosis is derived from the Greek word that signifies the dropping of leaves from the trees. This term
is applied to a group of characteristic structural and molecular events that separate this type of cell deletion from
necrosis. In contrast to necrosis that involves a group of cells simultaneously, apoptosis may occur in a
single cell surrounded by a group of viable cells. There is a distinct and precisely localized control over the fate of
specific cells in a mixed cell population that undergo apoptosis. Apoptosis is a selective process for deletion of
cells in various biological systems. This event similar to proliferation is tightly regulated with both
processes playing essential roles in the homeostasis of renewable tissues.
Diverse groups of molecules are involved in the apoptosis pathway. One set of mediators implicated in apoptosis belong to the asparate-specific cysteinyl proteases or caspases. A member of this family, caspase-3 (CPP32, apopain, YAMA) has been identified as being a key mediator of apoptosis of mammalian cells. Kothakota et al, screened the translation products of a murine protein library to find the substrates that are susceptible to cleavage by caspase-3. They found that in cells exposed to Fas, gelsolin was cleaved in vivo in a caspase dependent manner. The cleaved fragments of gelsolin led to the cleavage of the actin filaments in a Ca2+ independent manner. The expression of the gelsolin fragments also led to the apoptosis of cells. Additional evidence for the role of gelsolin in apoptosis was provided by showing that, as compared with wild-type neutrophis, those from mice lacking gelsolin exhibited a delayed onset of induced apoptosis. Therefore, the authors suggested that cleaved fragments of gelsolin may be implicated in apoptosis.
REFERENCE:
Kothakota S et al: Caspase 3-generated fragment of gelsolin: effector of morphological change in apoptosis.Science 278, 294-298, 1997
Figure 1. Sequences of events in caspase-3 mediated apoptosis
|



Figure legends:Top: Animation of apoptosis. Apoptotic bodies are released from an apoptotic cell. Middle: Hematoxylin-eosin stained section of liver. Arrow points to an apoptotic body. Bottom: Ultrastructural feature of apoptotic cells. Arrowheads point to apoptotic cells. Apoptotic cells exhibit dense nuclei
|