How Cells Grow - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 575

Homeostasis involves a complex series of reactions, an ongoing process inside an organism
that calls for different types of cell signaling. Any impairment can cause a disease. For
example, dysregulation of signaling pathway has been implicated in several forms of cancer.
The pathway, which conveys an antiapoptotic signal, has been found to be activated in
pancreatic adenocarcinoma tissues.
PCD is an integral part of both plant and animal tissue development. Development of an
organ or tissue is often preceded by the extensive division and differentiation of a particular
cell, the resultant mass is then “pruned” into the correct form by apoptosis. Unlike necrosis,
cellular death caused by injury, apoptosis results in cell shrinkage and fragmentation. Such
shrinkage and fragmentation allow the cells to be phagocytosed and their components
reused without releasing potentially harmful intracellular substances such as hydrolytic
enzymes into the surrounding tissue.
The process of apoptosis is controlled by a diverse range of cell signals, which may orig-
inate either extracellularly (extrinsic inducers) or intracellularly (intrinsic inducers). Extracel-
lular signals may include toxins, hormones, growth factors, nitric oxide, or cytokines and
therefore must either cross the plasma membrane or transduce to effect a response. These
signals may positively (i.e. trigger) or negatively (i.e. repress, inhibit, or dampen) affect
apoptosis. (Binding and subsequent initiation of apoptosis by a molecule is termed positive
induction, whereas the active repression or inhibition of apoptosis by a molecule is termed
negative induction.)
A cell initiates intracellular apoptotic signaling in response to a stress, which may bring
about cell suicide. The binding of nuclear receptors by glucocorticoids, heat, radiation,
nutrient deprivation, viral infection, hypoxia, and increased intracellular calcium concentra-
tion, for example, by damage to the membrane, can all trigger the release of intracellular
apoptotic signals by a damaged cell. A number of cellular components, such as poly ADP
ribose polymerase, may also help regulate apoptosis.
Before the actual process of cell death is precipitated by enzymes, apoptotic signals
must cause regulatory proteins to initiate the apoptosis pathway. This step allows
apoptotic signals to cause cell death or the process to be stopped, should the cell no longer
need to die. Several proteins are involved, but two main methods of regulation have been
identified: targeting mitochondria functionality or directly transducing the signal via
adaptor proteins to the apoptotic mechanisms. Another extrinsic pathway for initiation
identified in several toxin studies is an increase in calcium concentration within a cell
caused by drug activity, which also can cause apoptosis via a calcium-binding protease
calpain.
PCD in plants has a number of molecular similarities to animal apoptosis, but it also
has differences, notably the presence of a cell wall and the lack of an immune system
which removes the pieces of the dead cell. Instead of an immune response, the dying
cell synthesizes substances to break itself down and places them in a vacuole which
ruptures as the cell dies. Whether this whole process resembles animal apoptosis closely
enough to warrant using the name apoptosis (as opposed to the more general PCD) is
unclear.
One can infer that cell death in multicellular organisms is a means to maintain the overall
health of the organism. The energy spent may be termed endogenous metabolism. This is
a magnification of endogenous metabolism in single cells.