Apoptosis(from the Greek words apo=from and ptosis=falling,)is a highly regulated biochemical mechanism of programmed cell death.
Between 50 -70 billion cells die each day due to apoptosis in the average human adult. For an average child between the age of 8-15 approximately 20-30 billion cells die a day.
German scientist Carl Vogt was first to describe the principle of apoptosis in 1842.
In 1972 Ker first introduced the term apoptosis in a publication.
The 2002 Nobel prize in medicine was awarded to Syndeney Brenner,Horvitz and John E.Sulstone for their work identifiying genes that control apoptosis.The gene were identified by studies in the Nematode C. elegans(CED4) and these same genes function in humans(APAF) for apoptosis.
There is a alignment between the nucleotide sequence of C.elegans and APAF.
Apoptosis can be normally noticed during embryogenesis,metamorphosis and aging.For example,the differentiation of human fingers in a developing embryo requires the cells between the fingers to initiate apoptosis so that the fingers could separate.
Apoptosis is needed to destroy cells infected with viruses, cells with damage DNA.
Caspase dependent apoptosis is inititate either by exrtinsc or intrinsic factors.
There are two main caspase dependent apoptotic pathway
The extrinsic or death receptor pathway
The intrinsic or mitochondrial pathway
Extra cellular signal molecules bind with cell surface receptors(termed death receptors).One typical example is a Fas receptor(FasR),a member of and FasRTNF receptor family.Its ligand is Fasl(Fatty acid synthetase ligand) expressed in cytotoxic t-lymphocytes and natural killer cells.
FasL binds FasR on the surface of a cell recruits the adptor protein, FADD(Fas-associated death domain).This occurs through interaction between the death domain of FADD and FasR.
The death effector domain(DED) of FADD active the caspase-8 from procaspase-8.
Caspase 8 activates execuitor caspases which cleave substrates within the cell.Nucleases are activated, chromosomal DNA is degraded and cell dies by apoptosis.
2. INTRODUCTION
Apoptosis(from the Greek words apo=from and
ptosis=falling,)is a highly regulated biochemical
mechanism of programmed cell death.
Between 50 -70 billion cells die each day due to
apoptosis in the average human adult. For an average
child between the age of 8-15 approximately 20-30 billion
cells die a day.
3. HISTORY
• German scientist Carl Vogt was first to
describe the principle of apoptosis in 1842.
• In 1972 Ker first introduced the term
apoptosis in a publication.
• The 2002 Nobel prize in medicine was
awarded to Syndeney Brenner,Horvitz and
John E.Sulstone for their work identifiying
genes that control apoptosis.The gene were
identified by studies in the Nematode C.
elegans(CED4) and these same genes
function in humans(APAF) for apoptosis.
4.
5. PURPOSE OF APOPTOSIS
• Apoptosis can be normally noticed
during
embryogenesis,metamorphosis and
aging.For example,the
differentiation of human fingers in a
developing embryo requires the
cells between the fingers to initiate
apoptosis so that the fingers could
separate.
• Apoptosis is needed to destroy
cells infected with viruses, cells
with damage DNA.
7. CASPASE(Cysteine dependent aspartet
specific protease)
Caspases have proteolytic activity.They contain a key
cysteine residue in the catalytic site and selectively cleave
proteins at sites just C-terminal to asparate residues.
Two types of caspase are there based on their rolls in
apoptosis
Initiator caspase : caspase-2,-8,-9,-10
Executioner caspase : caspase-3,-6,-7
8.
9. Mechanism of apoptosis
• Caspase dependent apoptosis is inititate either by
exrtinsc or intrinsic factors.
There are two main caspase dependent apoptotic
pathway
◦ The extrinsic or death receptor pathway
◦ The intrinsic or mitochondrial pathway
10. Caspase dependent extrinsic apoptotic
pathway
•Extra cellular signal molecules bind with cell surface receptors(termed death
receptors).One typical example is a Fas receptor(FasR),a member of and
FasRTNF receptor family.Its ligand is Fasl(Fatty acid synthetase ligand)
expressed in cytotoxic t-lymphocytes and natural killer cells.
•FasL binds FasR on the surface of a cell recruits the adptor protein, FADD(Fas-
associated death domain).This occurs through interaction between the death
domain of FADD and FasR.
•The death effector domain(DED) of FADD active the caspase-8 from
procaspase-8.
•Caspase 8 activates execuitor caspases which cleave substrates within the
cell.Nucleases are activated, chromosomal DNA is degraded and cell dies by
apoptosis.
11.
12. DISEASES
A normal cell undergoes regulated division,differentiation and apoptosis,
when cells have lost the ususal control over their devision,differentiation and
apoptosis they become tumor cells.A tumor cell is the result of an abnormal
proliferation of cells without differentiation and apoptosis.
Uncontrolled apoptosis lead to atrophy, neurodegenerative
diseases,hematologic diseases and tissue damage.