Apoptosis

Apoptosis is a form of programed cell death in multicellular organisms

It is one of the main tyes of programed cell death and involve biochemical event leading to a
characteristics cell morphology and death. In more specific terms, it’s a series of biochemical
activites or events that lead to variety of morphological changes including changes in cell membrane
suchas loss of membrane asymmetry, cell shrinkage, nuclear fragmentation, chromatin condensation
and chromosome DNA fragmentation.

About 50-70 billions cells die each day due to apoptosis in human adult

For average age of 8-14 for children, approximately 20-30 billions cells die each day

Excessive apoptosis causes hypotrophy such as ischemic damage, whereas an insufficient amount
result in uncontrolled cell proliferation such as cancer

Why we need apoptosis

- It is part of development
- Elimination of infected cancerous cell

Differences between Apoptosis and Necrosis

AP- programmed cell death

Occurs through shrinking of cytoplasm followed by nucleus condensation

Natural physiological processes

Blebbing of plasma membrane is observed without losing integrity

Nec- Premature cell death

Swelling of cytoplasm along with mitochondrial followed by cell lysis

Pathological process which is caused by external ogans like toxins and infections

Membrane integrity is loosened

Roles of Caspases in apoptosis

- Cut off contact with the surrounding cell

- Recognise cytoskeleton
- Disrupt nuclear structure
- Induce cells to display signals marking it for phagocytosis
- Disintegrate cells into apoptotic body

TYPES OF CASPASES

Those involved in apoptosis

1. Initiator: initiate downsteam effctor caspases to initiate activation caspases. This includes
Caspase 2, caspase 9, caspase 8, caspase 10
2. Effector: cleaves target proteins resulting in morphological and biochemical markers of
apoptosis. They include Caspase 3, CASPASE 6, caspase 7 and 8

Intrinsic and extrinsic pathways in apoptosis

The process of apoptosis is controlled by a diverse range of cell signals, which may originate
either extracellular or intracellularly

Extracellular include hormones, growth factors, cytokines and therefore must either cross the
plasma membrane or produce response. These signals may be positively or negatively induce
apoptosis; in the the context, the binding and subsequent initiation of apoptosis by a molecule is
termed positive where as the active repression of apoptosis by a molecule is termed negative.

Intrinsic apoptosis includes signalling is a response initiated by a cell in response to stress and
may ultimately result in cell suicide. He bindingof receptor by heat, radiation, nutrient
deprivation, viral infection are all factors that can lead to the release of intracellular apoptotic
signals by a damaged cell.

Apoptosis in cancer

Apoptosis also plays role in preventing cancer, if a cell is unable to undergo apoptosis, due to
mutation or biochemical inhibition, it can continue dividing and develop into tumor. For
ezample, infection of HPV causes a gene to interfere with the cells p53 protein, an important
member of the apoptotic pathway. This interfere in the apoptotic capability of the cells play a
critical role in the devt. Of cervical cancer

Apoptosis proteins that target nitochondrion affect nthem in different ways: they may be
mitochondrial swelling through the formaton of membrane pores or they may increase the
permeability of the mtd membrane and causes apoptotic effectors to leak out

Cytochrome c is released from mtd due to formation of a channel Mac, in the outer
mitochondrial membrane and serve a regulatory function as it precedes morphologicalchange in
associated with apotosis . cytochrome c is released and binds wth Apaf-1 and Atp, which then
bind to pro-caspase 9 to create a protein complex known as a apoptosome. The apoptosome
cleanses procapcase to its active formof caspsase 9 which in turn ativiates the efectors caspase 3

Evidence of genetic component for thr pathogeness of human cancer

Mutation rate

XERPDERMA PIGMENTOUM

Bloom syndrome – uv light

AT - XRAY