The cutting edge: apoptosis and therapeutic opportunity - Artificial Cells, Cell Engineering and Therapy - page 117

5
The cutting edge:
apoptosis and therapeutic opportunity

C GRIFFIN, D GUEORGUIEVA, A McLACHLAN-
BURGESS, M SOMAYAJULU-NITU and S PANDEY,
University of Windsor, Canada

5.1 Apoptosis

Programmed cell death is an important physiological process that plays a sig-
nificant role during the development and maintenance of the living organisms.
Two distinct categories of cell death processes, namely apoptosis and necrosis,
have been defined (Kerr et al., 1972). Necrosis represents pathological cell death
characterized by the swelling of the cells and organelles and lysis of the plasma
membrane. Apoptosis, on the other hand, is characterized by plasma membrane
blebbing, cell shrinkage, condensation of chromatin and DNA fragmentation
into high molecular weight and/or oligonucleosomal fragments. Thus, cells
undergoing apoptosis systematically fragment their DNA, shrink from within
and get disposed of quietly by phagocytosis without causing any inflammation
or damage to their surroundings. While apoptosis is a normal cellular event
during development, it can also be induced by pathological conditions and
injuries. Apoptosis is involved in a wide range of pathologies including viral
diseases, neurodegeneration, cancer and aging.
Apoptosis is a genetically regulated cellular process that can be switched on
or off depending on the ratio of pro-apoptotic to anti-apoptotic factors. In the
past two decades significant progress has been made to elucidate the bio-
chemical mechanism of apoptosis. Various proteins and other stimuli actively
participating in the initiation and execution of apoptosis have been identified.
Two major pathways, namely the extrinsic pathway involving a cell death
receptor-induced mechanism and the intrinsic pathway involving mitochondrial
permeabilization-apoptosome mediated pathway, have been proposed.
In the receptor-mediated apoptosis pathway (Fig. 5.1), interaction of ligands
such as Fas, TNF and TRAIL with their specific cell surface receptor is followed
by oligomerization of these receptors and their association with and recruitment
of various proteins on the cytosolic side of the plasma membrane. This complex
is referred to as death inducing signalling complex (DISC) (Ashkenzai and
Dixit, 1998). One of the main consequences of DISC formation is the activation