GROWTH FACTORS

 A growth factor, as initially defined, is a secreted

biologically active molecule that can affect the
growth of cells.
 The may be...
1.Cytokines. 2. Hormones
These factors bind with specific surfac receptors of
target cell and stimulate proliferation
differentiation and/or maturation of these cells
 Growth factor and cytokine are almost same term
but their functions are different...
 Growth factors act on the cells of growing tissue
But cytokines are concerned with cells of immune
syste and hematopoietic cells.
Source and primary actions of growth
factors...
Cell Death → This occurs by three distinct processes

1. AUTOPHAGY
2. APOPTOSIS
3. NECROSIS
 1. AUTOPHAGY →

• Autophagy is your body's cellular recycling system.

. It allows a cell to disassemble its junk parts and

repurpose the salvageable bits and pieces into new,
usable cell parts.

. A cell can discard the parts it doesn't need. .

. Autophagy is also quality control for your cells.

 Autophagy is a normal physiological process in the
body by which cells are destroyed.
 The word autophagy is derived from Greek (auto =
self, phagy = eating).
 It is also called autophagocytosis
 Autophagy involves formation of autophagosome
which contains worn-out cytoplasmic organelles.
 Autophagosome fuses with lysosome then the
enzymes of lysosome destroy the organelles by
protein degradation.
 Remaining usefull part of the organelles are reused for
formation of new cells.
 Thus, it maintains a balance between break down of
damaged organelles and formation new cellular
organelles.
 Example --: Cancer cell.
Alternate day fasting.
 2. Apoptosis

 Apoptosis is defined as the natural or programmed

death of the cell under genetic control.
 Originally, apoptosis refers to the process by which
leaves fall from trees in autumn (In Greek, apoptosis
means 'falling leaves.
 Apoptosis is referred as 'cell suicide' because the cells
activate an intracellular death program and kill
themselves in a controlled way.
 Apoptosis is a normal phenomenon and it is
essential for normal development of the body.
 apoptosis usually does not produce
inflammatory reactions in the neighboring
tissues.
 The main Purpose of apoptosis is to remove
unwanted cells without causing any stress or
damage to the neighboring cells.
Functional significance →

1.Apoptosis plays a vital role in cellular

homeostasis.
2. It is useful for removal of a cell that is
damaged beyond repair by a virus or a toxin.
3. It is an essential event during development
and in adult stage.
Examples →
 Largenumber of neurons are produced during
development of central nervous system. But 50% of
neurons are removed by apoptosis during the
formation of synapses between neurons.ii.
 Apoptosis is responsible for the removal of tissues
of webs between fingers and toes during
developmental stage in fetus.
 Regression and disappearance of duct system
during sex differentiation in fetus.
 Cell that loses the contact with neighboring
cells OR basal lamina in epithelial tissue dies
by apoptosis.
 This is essential for death of old enterocytes
that shed into the lumen of intestinal glands.
 It plays an important role in cyclic sloughing
of the inner layer of endometrium, resulting
in menstruation.
 Itremoves the auto aggressive T cells and
prevent human body from autoimmune
disease.
Activation of Apoptosis →
 It happens by two signals.
1. Withdrawal of positive signals→
 Positive signals are the signals which are
necessary fo long-time survival of cells.
Positive signals are continuous produced by
other cells or some chemical stimulant.
 Absence or withdrawal of the positive signals
activate apoptosis.
2. Arrival of negative signals→
 Negative signals are the external or internal
stimuli which initiate apoptosis.
 External stimuli are applied by stimuls
molecules, death-receptor ligands.
 Internal stimuli are arising from inside the cell
 Death receptor ligands→
 Death-receptor ligands are substances which
bind with specific cell membrane receptors
and initiate the process of apoptosis. These
are mainly three types.
(i) Tumor necrosis factor alpha (TNF-α)
(ii) Fas ligand (FASL)
TRAIL Ligand
(iii)
 TNF-related apoptosis inducing legand
(TRAIL) receptors called DR4 & DR5.
Initiation of Apoptosis →It follows two
distinct pathway...

1. Extrinsic. 2. Intrinsic
 Both the pathway lead to an execution process
which is responsible for cell death.
 In extrinsic pathway, the signal (stimulus) for
apoptosis is received from outside the cell.
 In intrinsic pathway, the signal arises from within
cell itself.
Extrinsic pathway of apoptosis
 Extrinsic pathway of apoptosis is initiated by the
stimulation of death receptors of target cells by
death ligands.
 Generally, death receptors have an extracellular
domain and an intracellular (cytoplasmic) domain.
 Extracellular domain is responsible for binding of
ligands and interaction with those ligands.
 The intracellular domain is called death domain.
When the ligand binds with receptor, death domain
allows recruitment of many proteins and formation
of a protein complex.
 The protein complex is said to be death
inducing signaling complex (DISC).
 Now caspase is recruited to DISC and gets
activated resulting in execution process.

Extrinsic pathway→ Death legand →

Death receptor → Caspases →
Nuclease/Protease → Cell Death
 Intrinsic pathway of apoptosis

 It is initiated by these conditions...

 1. Cellular stress.
 2. Increase in the concentration of intracellular
oxidants.
 3. Viral infection.
 4. Damage of DNA.
 Internalstimuli activate the proapoptotic
BCL-2 family proteins which in turn
inactivate antiapoptotic BCL-2 proteins.
 Interaction between proapoptotic and
antiapoptotic proteins causes destabilization
of mitochondrial membrane and release of
apoptotic factors which induce execution
process.
 BCL-2(B-cell lymphoma 2) family proteins
are the cell death regulators located near
mitochondria.